TY  - JOUR
AU  - Milenković, Mila
AU  - Ciasca, Gabriele
AU  - Bonasera, Aurelio
AU  - Scopelliti, Michelangelo
AU  - Marković, Olivera
AU  - Verbić, Tatjana
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
PY  - 2024
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7093
AB  - The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L-cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic 
resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs 
combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.
PB  - Elsevier
T2  - Journal of Photochemistry and Photobiology, B: Biology
T1  - Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects
VL  - 250
SP  - 112818
DO  - 10.1016/j.jphotobiol.2023.112818
ER  - 

@article{
author = "Milenković, Mila and Ciasca, Gabriele and Bonasera, Aurelio and Scopelliti, Michelangelo and Marković, Olivera and Verbić, Tatjana and Todorović Marković, Biljana and Jovanović, Svetlana",
year = "2024",
abstract = "The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent. Gamma irradiation was employed as a tool to achieve one-step modification of GQDs in the presence of L-cysteine amino acid as a source of heteroatoms. X-ray Photoelectron Spectroscopy (XPS), nuclear magnetic 
resonance (NMR), and zeta potential measurements provided the necessary data to clarify the structure of modified dots and verify the introduction of both S- and N-atoms in GQDs structure, but also severe changes in the aromatic, sp2 domains. Namely, γ-irradiation caused a bonding of S atoms in 1.14 at.% mainly as thiol groups, and N in 1.81 at.% as amino groups, but sp2 contribution in GQD structure was lowered from 63.00 to 4.86 at.%, as measured in dots irradiated at a dose of 200 kGy. Fluorescence quenching measurements showed that L-cysteine-modified dots are able to bind to human serum albumin. The antibacterial activity of GQDs 
combined with 1 and 6 h of blue light (470 nm) irradiation was tested against 8 bacterial strains. GQD-cys-25 sample provided the best results, with minimum inhibitory concentration (MIC) as low as 125 μg/mL against S. aureus, E. faecalis, and E. coli after only 1 h of blue light exposure.",
publisher = "Elsevier",
journal = "Journal of Photochemistry and Photobiology, B: Biology",
title = "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects",
volume = "250",
pages = "112818",
doi = "10.1016/j.jphotobiol.2023.112818"
}

Milenković, M., Ciasca, G., Bonasera, A., Scopelliti, M., Marković, O., Verbić, T., Todorović Marković, B.,& Jovanović, S.. (2024). Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects. in Journal of Photochemistry and Photobiology, B: Biology
Elsevier., 250, 112818.
https://doi.org/10.1016/j.jphotobiol.2023.112818

Milenković M, Ciasca G, Bonasera A, Scopelliti M, Marković O, Verbić T, Todorović Marković B, Jovanović S. Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects. in Journal of Photochemistry and Photobiology, B: Biology. 2024;250:112818.
doi:10.1016/j.jphotobiol.2023.112818 .

Milenković, Mila, Ciasca, Gabriele, Bonasera, Aurelio, Scopelliti, Michelangelo, Marković, Olivera, Verbić, Tatjana, Todorović Marković, Biljana, Jovanović, Svetlana, "Blue-light-driven photoactivity of L-cysteine-modified graphene quantum  dots and their antibacterial effects" in Journal of Photochemistry and Photobiology, B: Biology, 250 (2024):112818,
https://doi.org/10.1016/j.jphotobiol.2023.112818 . .

TY  - JOUR
AU  - Pešić, Miloš
AU  - Krstić, Jugoslav
AU  - Verbić, Tatjana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5612
AB  - Molecularly imprinting technology was applied for preparing selective sorbents for benzophenone-4 (BP4), an organic UV filter used in sun-screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spectroscopy, elemental analysis, conductometric titrations and nitrogen physisorption at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydibenzo-ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency.
AB  - Технологија молекулског обележавања примењена је у синтези селективних сорбената за бензофенон-4 (BP4), органски UV филтер који се користи у кремама за сунчање  и другим козметичким производима. Полимери су добијени полимеризацијом у маси, користећи (BP4) као матрицу. Комбинацијом стабилности (механичке и хемијске),  селективности и робусности молекулски обележених полимера са својствима BP4  извршено је успешно обележавање (фактор обележавања 1,05–2,60). Карактеризација  добијених полимера је извршена применом инфрацрвене спектроскопије, елементалне  анализе, кондуктометријских титрација и физисорпције азота на 77 К. Адсорпциони  капацицети и селективност испитани су за 7 других органских UV филтера (бензофенон-3, бензофенон-8, хомосалат, бутилметоксидибензоилметан, етилхексил-салицилат,  етилхексил-р-диметиламинобензоат и етилхексил-р-метоксицинамат), потврђујући  велики адсорпциони капацитет и високу селективност за везивање BP4. Највећи адсорпциони капацитет показао је ко-полимер 4-винилпиридина и дивинилбензена добијен  коришћењем диметил-сулфоксида као порогена (1,108 mmol/g). Полимер са највећим  капацицетом за везивање BP4 примењен је као сорбент за екстракцију чврстом фазом  BP4 из водених раствора са ефикасношћу од 98,5 %.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Highly selective water-compatible molecularly imprinted polymers for benzophenone-4
T1  - Високо селективни водокомпатибилни молекулски обележени полимери за бензофенон-4
VL  - 88
IS  - 1
SP  - 55
EP  - 68
DO  - 10.2298/JSC22032540P
ER  - 

@article{
author = "Pešić, Miloš and Krstić, Jugoslav and Verbić, Tatjana",
year = "2023",
abstract = "Molecularly imprinting technology was applied for preparing selective sorbents for benzophenone-4 (BP4), an organic UV filter used in sun-screens and cosmetics. Several imprinted polymers were prepared by bulk polymerization, using BP4 as template. Combination of stability (mechanical and chemical), selectivity and robustness of the imprinted polymers with BP4 properties resulted in a successful imprinting process (imprinting factors in range 1.05–2.60). The prepared polymers were characterised by infrared spectroscopy, elemental analysis, conductometric titrations and nitrogen physisorption at 77 K. Adsorption capacities and selectivity towards 7 other organic UV filters (benzophenone-3, benzophenone-8, homosalate, butyl methoxydibenzo-ylmethane, ethyl hexyl salicylate, ethyl hexyl p-dimethylamino benzoate and ethyl hexyl p-methoxycinnamate) were determined, proving high adsorption capacity and high selectivity for BP4 binding. The highest adsorption capacity was observed for 4-vinylpyridine/ethylene glycol dimethacrylate co-polymer prepared in dimethyl sulfoxide (1.108 mmol g-1). The imprinted polymer with the highest binding capacity was applied to solid phase extraction of BP4 from aqueous solutions with 98.5 % efficiency., Технологија молекулског обележавања примењена је у синтези селективних сорбената за бензофенон-4 (BP4), органски UV филтер који се користи у кремама за сунчање  и другим козметичким производима. Полимери су добијени полимеризацијом у маси, користећи (BP4) као матрицу. Комбинацијом стабилности (механичке и хемијске),  селективности и робусности молекулски обележених полимера са својствима BP4  извршено је успешно обележавање (фактор обележавања 1,05–2,60). Карактеризација  добијених полимера је извршена применом инфрацрвене спектроскопије, елементалне  анализе, кондуктометријских титрација и физисорпције азота на 77 К. Адсорпциони  капацицети и селективност испитани су за 7 других органских UV филтера (бензофенон-3, бензофенон-8, хомосалат, бутилметоксидибензоилметан, етилхексил-салицилат,  етилхексил-р-диметиламинобензоат и етилхексил-р-метоксицинамат), потврђујући  велики адсорпциони капацитет и високу селективност за везивање BP4. Највећи адсорпциони капацитет показао је ко-полимер 4-винилпиридина и дивинилбензена добијен  коришћењем диметил-сулфоксида као порогена (1,108 mmol/g). Полимер са највећим  капацицетом за везивање BP4 примењен је као сорбент за екстракцију чврстом фазом  BP4 из водених раствора са ефикасношћу од 98,5 %.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Highly selective water-compatible molecularly imprinted polymers for benzophenone-4, Високо селективни водокомпатибилни молекулски обележени полимери за бензофенон-4",
volume = "88",
number = "1",
pages = "55-68",
doi = "10.2298/JSC22032540P"
}

Pešić, M., Krstić, J.,& Verbić, T.. (2023). Highly selective water-compatible molecularly imprinted polymers for benzophenone-4. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 88(1), 55-68.
https://doi.org/10.2298/JSC22032540P

Pešić M, Krstić J, Verbić T. Highly selective water-compatible molecularly imprinted polymers for benzophenone-4. in Journal of the Serbian Chemical Society. 2023;88(1):55-68.
doi:10.2298/JSC22032540P .

Pešić, Miloš, Krstić, Jugoslav, Verbić, Tatjana, "Highly selective water-compatible molecularly imprinted polymers for benzophenone-4" in Journal of the Serbian Chemical Society, 88, no. 1 (2023):55-68,
https://doi.org/10.2298/JSC22032540P . .

TY  - CONF
AU  - Verbić, Tatjana Ž.
AU  - Avdeef, Alex
AU  - Tam, Kin Y.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Topalović, Igor A.
AU  - Veljković, Dušan Ž.
AU  - Kathawala, Mufaddal
AU  - Serajuddin, Abu T. M.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6567
AB  - Since the introduction of combinatorial chemistry and high-throughput screening in drug 
discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically 
while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo 
complicated reactions in aqueous solution, such as forming precipitates or complexes with 
buffer species or undergoing self-aggregation (dimer, trimer, etc.) or micelle formations. 
Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of 
ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, 
determined by a suitable method. In a pH-dependent measurement of a property (e.g. 
solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the 
true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking 
place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of 
measured values, but paradoxically, such preference can lead to inaccurate rationalization of 
the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can 
be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, 
the use of calculated pKas can substantially wrench the interpretation of solution properties. 
Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 
40 years, exhibits some of the properties of relatively recent drug molecules by being 
extremely water insoluble and having variable pKa values reported. We have recently 
combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water 
cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base 
dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along 
the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to 
water, the dimer would be more water soluble than the monomeric free base. In saturated 
solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the 
dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the 
behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount 
importance for understanding of CFZ speciation and the future progress in developing its 
improved formulations which is the subject of our ongoing studies.
PB  - International Association of Physical Chemists
C3  - Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia
T1  - Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH
SP  - 15
EP  - 15
UR  - https://hdl.handle.net/21.15107/rcub_cer_6567
ER  - 

@conference{
author = "Verbić, Tatjana Ž. and Avdeef, Alex and Tam, Kin Y. and Marković, Olivera S. and Pešić, Miloš P. and Topalović, Igor A. and Veljković, Dušan Ž. and Kathawala, Mufaddal and Serajuddin, Abu T. M.",
year = "2023",
abstract = "Since the introduction of combinatorial chemistry and high-throughput screening in drug 
discovery in the early 1990s, the solubility of new chemical entities (NCE) decreased drastically 
while their lipophilicities increased greatly. Characterizing physicochemical properties of low soluble molecules can be especially challenging, since such molecules can undergo 
complicated reactions in aqueous solution, such as forming precipitates or complexes with 
buffer species or undergoing self-aggregation (dimer, trimer, etc.) or micelle formations. 
Most drugs are ionizable. Foremost to the rational interpretation of solution behavior of 
ionizable drugs in a physiologically-relevant pH domain requires an accurate aqueous pKa, 
determined by a suitable method. In a pH-dependent measurement of a property (e.g. 
solubility-, lipophilicity-, permeability-pH), when the apparent pKa value is different from the 
true aqueous pKa value, it may be an early clue that nonideal solution behavior may be taking 
place. In pharmaceutical research, it may seem cost-effective to use calculated pKa instead of 
measured values, but paradoxically, such preference can lead to inaccurate rationalization of 
the pH-dependent behavior of the drug molecule. For simple molecules, calculated values can 
be useful, but for today’s new drugs or for molecules prone to complicated solution behavior, 
the use of calculated pKas can substantially wrench the interpretation of solution properties. 
Clofazimine (CFZ), although discovered about 66 years ago, and used therapeutically for nearly 
40 years, exhibits some of the properties of relatively recent drug molecules by being 
extremely water insoluble and having variable pKa values reported. We have recently 
combined potentiometric titrations and UV/Vis spectrophotometry in methanol-water 
cosolvent media, accompanied by DFT calculations, to assess the hypothesis of CFZ free base 
dimerization. We reasoned that a soluble dimer might form from drug-drug adhesion along 
the hydrophobic molecular surface. With lessened exposure of the hydrophobic surface to 
water, the dimer would be more water soluble than the monomeric free base. In saturated 
solutions, the apparent solubility in alkaline pH would be elevated due to the presence of the 
dimer. The effect of that would be a lower pKa and reverse pKa cosolvent dependence – the 
behaviour we have noticed in CFZ aqueous solutions. These findings are of paramount 
importance for understanding of CFZ speciation and the future progress in developing its 
improved formulations which is the subject of our ongoing studies.",
publisher = "International Association of Physical Chemists",
journal = "Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia",
title = "Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH",
pages = "15-15",
url = "https://hdl.handle.net/21.15107/rcub_cer_6567"
}

Verbić, T. Ž., Avdeef, A., Tam, K. Y., Marković, O. S., Pešić, M. P., Topalović, I. A., Veljković, D. Ž., Kathawala, M.,& Serajuddin, A. T. M.. (2023). Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH. in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia
International Association of Physical Chemists., 15-15.
https://hdl.handle.net/21.15107/rcub_cer_6567

Verbić TŽ, Avdeef A, Tam KY, Marković OS, Pešić MP, Topalović IA, Veljković DŽ, Kathawala M, Serajuddin ATM. Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH. in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia. 2023;:15-15.
https://hdl.handle.net/21.15107/rcub_cer_6567 .

Verbić, Tatjana Ž., Avdeef, Alex, Tam, Kin Y., Marković, Olivera S., Pešić, Miloš P., Topalović, Igor A., Veljković, Dušan Ž., Kathawala, Mufaddal, Serajuddin, Abu T. M., "Revealing the story of an orphan drug: clofazimine speciation  and solubilization as a function of pH" in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia (2023):15-15,
https://hdl.handle.net/21.15107/rcub_cer_6567 .

TY  - CONF
AU  - Topalović, Igor A.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Kathawala, Mufaddal
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana Ž.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6566
AB  - Methods for drug solubilization have become important part of modern drug discovery and 
development due to increasing number of extremely insoluble drugs and drug candidates. 
One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly 
basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy
and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2].
We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. 
The aim of the present study was to investigate CFZ solubilization using the ABS approach. 
Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, 
malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids 
showed some solubilization effect. The effect of their concentration (and the solution pH 
value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions 
in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 
24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The 
CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ 
solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), 
from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect 
of CFZ solubilization is much more pronounced when the acid concentration is raised above 
2 M. These results can be used as the basis for further CFZ formulation optimization.
Furthermore, our ongoing research is focused on the type of interactions and other possible 
factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solubilization as a general methodology in drug design and development.
PB  - International Association of Physical Chemists
C3  - Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia
T1  - Clofazimine acid-base solubilization: influence  of small organic acids’ concentration
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_cer_6566
ER  - 

@conference{
author = "Topalović, Igor A. and Marković, Olivera S. and Pešić, Miloš P. and Kathawala, Mufaddal and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana Ž.",
year = "2023",
abstract = "Methods for drug solubilization have become important part of modern drug discovery and 
development due to increasing number of extremely insoluble drugs and drug candidates. 
One of such methods is acid-base supersolubilization (ABS) [1]. Clofazimine (CFZ) is weakly 
basic antibiotic and anti-inflammatory drug, most notably used in the treatment of leprosy
and tuberculosis, with recently proven inhibitory activity against several coronaviruses [2].
We have recently unraveled its aqueous pKa value and its unique cosolvent dependence [3]. 
The aim of the present study was to investigate CFZ solubilization using the ABS approach. 
Eight small organic acids were tested for the ABS effect (glutaric, malic, tartaric, citric, 
malonic, maleic, succinic, adipic) but only glutaric (GA), malic (MA), and tartaric (TA) acids 
showed some solubilization effect. The effect of their concentration (and the solution pH 
value) was further tested. The solubility of CFZ was determined in GA, MA, and TA solutions 
in wide concentration (1.0×10-2 – 5.0 M) and pH range (~0.2 – 4.8). Equilibration time was 
24 hours (6 h of stirring + 18 h of sedimentation). Phases were separated by filtration. The 
CFZ concentration in supernatant was determined by HPLC-UV/VIS. Results show that CFZ 
solubility increases as acid concentration increases: from 3.04×10-3 to 10.68 mg/mL (in GA), 
from 9.06×10-3 to 1.23 mg/mL (in MA) and from 4.76×10-3 to 0.32 mg/mL (in TA). The effect 
of CFZ solubilization is much more pronounced when the acid concentration is raised above 
2 M. These results can be used as the basis for further CFZ formulation optimization.
Furthermore, our ongoing research is focused on the type of interactions and other possible 
factors that can influence CFZ and other prectically insoluble drugs, embracing (super)solubilization as a general methodology in drug design and development.",
publisher = "International Association of Physical Chemists",
journal = "Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia",
title = "Clofazimine acid-base solubilization: influence  of small organic acids’ concentration",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_cer_6566"
}

Topalović, I. A., Marković, O. S., Pešić, M. P., Kathawala, M., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T. Ž.. (2023). Clofazimine acid-base solubilization: influence  of small organic acids’ concentration. in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia
International Association of Physical Chemists., 66-66.
https://hdl.handle.net/21.15107/rcub_cer_6566

Topalović IA, Marković OS, Pešić MP, Kathawala M, Serajuddin ATM, Avdeef A, Verbić TŽ. Clofazimine acid-base solubilization: influence  of small organic acids’ concentration. in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia. 2023;:66-66.
https://hdl.handle.net/21.15107/rcub_cer_6566 .

Topalović, Igor A., Marković, Olivera S., Pešić, Miloš P., Kathawala, Mufaddal, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana Ž., "Clofazimine acid-base solubilization: influence  of small organic acids’ concentration" in Book of Abstracts - 10th IAPC Meeting: Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK, September 4-6, 2023, Belgrade, Serbia (2023):66-66,
https://hdl.handle.net/21.15107/rcub_cer_6566 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
AU  - Rašeta, Milena
AU  - Verbić, Tatjana
AU  - Marković, Olivera
AU  - Matijević, Borko
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5151
AB  - Карбохидразони и њихови тио-аналози представљају
једињења добијена кондензацијом карбохидразида, односно тиокарбохи-
дразида са карбонилним једињењима. Захваљујући њиховој структури,
релативно једноставној синтези и великој реактивности, поменути дери-
вати имају широк спектар примене у свим сферама. У оквиру овог рада,
за четири новосинтетисана моно(тио)карбохидразона, одређене су кисе-
линске константе применом потенциметријске методе. Такође, методом
линеарне корелације енергија солватације и применом Catalan-овог моде-
ла испитан је утицај специфичних и неспецифичних међумолекулских
интеракција на померања у UV-Vis апсорпционим спектрима. У циљу
испитивавања потенцијалне биолошке активности 2 - пиридин-(тио) кар-
бохидразона, применом DPPH теста, одређен је њихов антиоксидативни
потенцијал и закључено је да су деривати тиокарбохидразона значајно
активнији у односу на карбохидразоне.
AB  - Carbohydrazones and their thio analogs represent compounds
obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl
compounds. Due to their structure, relatively simple synthesis, and high
reactivity, mentioned derivatives have a wide range of applications in all fields.
In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method.
Also, the influence of specific and nonspecific intermolecular interactions
on maxima shifting in UV-Vis absorption spectra was investigated and quantified
using the linear solvation energy relationships method and Catalan’s model.
Finally, by applying the DPPH assay, the antioxidant potential of the newly
synthesized compounds was determined, and thiocarbohydrazone derivatives
proved to be significantly more active when compared to carbo-hydrazones.
PB  - Banja Luka : Akademija nauka i unjetnosti Republike Srpske
C3  - Савремени материјали -  зборник радова / Contemporary Materials - proceedings
T1  - Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives
T1  - Испитивање физичко-хемијских својстава и потенцијалне биолошке активности деривата 2-пиридин-(тио) карбохидразона
UR  - https://hdl.handle.net/21.15107/rcub_cer_5151
ER  - 

@conference{
author = "Mrđan, Gorana and Vaštag, Đenđi and Apostolov, Suzana and Rašeta, Milena and Verbić, Tatjana and Marković, Olivera and Matijević, Borko",
year = "2022",
abstract = "Карбохидразони и њихови тио-аналози представљају
једињења добијена кондензацијом карбохидразида, односно тиокарбохи-
дразида са карбонилним једињењима. Захваљујући њиховој структури,
релативно једноставној синтези и великој реактивности, поменути дери-
вати имају широк спектар примене у свим сферама. У оквиру овог рада,
за четири новосинтетисана моно(тио)карбохидразона, одређене су кисе-
линске константе применом потенциметријске методе. Такође, методом
линеарне корелације енергија солватације и применом Catalan-овог моде-
ла испитан је утицај специфичних и неспецифичних међумолекулских
интеракција на померања у UV-Vis апсорпционим спектрима. У циљу
испитивавања потенцијалне биолошке активности 2 - пиридин-(тио) кар-
бохидразона, применом DPPH теста, одређен је њихов антиоксидативни
потенцијал и закључено је да су деривати тиокарбохидразона значајно
активнији у односу на карбохидразоне., Carbohydrazones and their thio analogs represent compounds
obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl
compounds. Due to their structure, relatively simple synthesis, and high
reactivity, mentioned derivatives have a wide range of applications in all fields.
In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method.
Also, the influence of specific and nonspecific intermolecular interactions
on maxima shifting in UV-Vis absorption spectra was investigated and quantified
using the linear solvation energy relationships method and Catalan’s model.
Finally, by applying the DPPH assay, the antioxidant potential of the newly
synthesized compounds was determined, and thiocarbohydrazone derivatives
proved to be significantly more active when compared to carbo-hydrazones.",
publisher = "Banja Luka : Akademija nauka i unjetnosti Republike Srpske",
journal = "Савремени материјали -  зборник радова / Contemporary Materials - proceedings",
title = "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives, Испитивање физичко-хемијских својстава и потенцијалне биолошке активности деривата 2-пиридин-(тио) карбохидразона",
url = "https://hdl.handle.net/21.15107/rcub_cer_5151"
}

Mrđan, G., Vaštag, Đ., Apostolov, S., Rašeta, M., Verbić, T., Marković, O.,& Matijević, B.. (2022). Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in Савремени материјали -  зборник радова / Contemporary Materials - proceedings
Banja Luka : Akademija nauka i unjetnosti Republike Srpske..
https://hdl.handle.net/21.15107/rcub_cer_5151

Mrđan G, Vaštag Đ, Apostolov S, Rašeta M, Verbić T, Marković O, Matijević B. Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in Савремени материјали -  зборник радова / Contemporary Materials - proceedings. 2022;.
https://hdl.handle.net/21.15107/rcub_cer_5151 .

Mrđan, Gorana, Vaštag, Đenđi, Apostolov, Suzana, Rašeta, Milena, Verbić, Tatjana, Marković, Olivera, Matijević, Borko, "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives" in Савремени материјали -  зборник радова / Contemporary Materials - proceedings (2022),
https://hdl.handle.net/21.15107/rcub_cer_5151 .

TY  - JOUR
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4936
AB  - The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,2019), was applied. An improved and more detailed experimentaldesign of the Nor solubility measurement allowed us to exploit thefull capacity of the pH-RSF method. Complex equilibria in theaqueous phase (cationic and anionic complex formation betweenNor and the phosphate) and solid-phase transformations (Nor freebase, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)were characterized by a detailed analysis of the solubilitymeasurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustratethe influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in theformulation of drug products.
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
VL  - 19
IS  - 2
SP  - 710
EP  - 719
DO  - 10.1021/acs.molpharmaceut.1c00919
ER  - 

@article{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,2019), was applied. An improved and more detailed experimentaldesign of the Nor solubility measurement allowed us to exploit thefull capacity of the pH-RSF method. Complex equilibria in theaqueous phase (cationic and anionic complex formation betweenNor and the phosphate) and solid-phase transformations (Nor freebase, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)were characterized by a detailed analysis of the solubilitymeasurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustratethe influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in theformulation of drug products.",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints",
volume = "19",
number = "2",
pages = "710-719",
doi = "10.1021/acs.molpharmaceut.1c00919"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics
American Chemical Society (ACS)., 19(2), 710-719.
https://doi.org/10.1021/acs.molpharmaceut.1c00919

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics. 2022;19(2):710-719.
doi:10.1021/acs.molpharmaceut.1c00919 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints" in Molecular Pharmaceutics, 19, no. 2 (2022):710-719,
https://doi.org/10.1021/acs.molpharmaceut.1c00919 . .

TY  - CONF
AU  - Marković, Olivera S.
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5396
AB  - Experimental studies of solubility are important in all phases of drug design and development. Solubility data are used to screen out drug-like candidates, biopharmaceutical classification and formulation optimization. The development of oral and parenteral dosage forms can be challenging, especially when drugs are poorly soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions are present in drug suspension. The influence of different counterions on the existing equilibria and on pH-dependent drug solubility must be defined in such systems. To investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as a function of pH in the presence of both chloride and phosphate ions as well as in chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was used for solubility determination. The computer program pDISOL–X was used for data analysis. It is shown that distinct pH-dependent solubility profiles were obtained in studied systems. Depending on the pH and the total concentration of chloride and/or phosphate ions, Im can precipitate as chloride and phosphate salt or free base. Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 (chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). The intensive self-aggregation of Im in acidic region was suppressed by raising chloride or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was decreased due to the common-ion effect. This study illustrates the influence of competing counterions on Im solubility and on interconversions in solid phase. Hence, such factors must be taken into account during formulation optimization in drug research.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
T1  - The influence of competing counterions on the solubility of imipramine
SP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_cer_5396
ER  - 

@conference{
author = "Marković, Olivera S. and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "Experimental studies of solubility are important in all phases of drug design and development. Solubility data are used to screen out drug-like candidates, biopharmaceutical classification and formulation optimization. The development of oral and parenteral dosage forms can be challenging, especially when drugs are poorly soluble, ionizable, exhibiting pH-dependent solubility and when multiple counterions are present in drug suspension. The influence of different counterions on the existing equilibria and on pH-dependent drug solubility must be defined in such systems. To investigate the effect of multiple ions on the solubility of a model basic drug – tricyclic antidepressant imipramine (Im), we conducted a systematic study of the Im solubility as a function of pH in the presence of both chloride and phosphate ions as well as in chloride-free and phosphate-free suspensions. The pH–Ramp shake–flask method1,2 was used for solubility determination. The computer program pDISOL–X was used for data analysis. It is shown that distinct pH-dependent solubility profiles were obtained in studied systems. Depending on the pH and the total concentration of chloride and/or phosphate ions, Im can precipitate as chloride and phosphate salt or free base. Furthermore, pH values of solid phase transitions (pHmax) varied as well. For instance, pHmax of solid phase transition of (ImH)H2PO4(s) to (ImH)2HPO4(s) change from 5.15 (chloride and phosphate-containing suspensions) to 5.73 (chloride-free suspensions). The intensive self-aggregation of Im in acidic region was suppressed by raising chloride or phosphate ions concentration (Iavg 1.42–1.64 M). In that way, solubility of Im was decreased due to the common-ion effect. This study illustrates the influence of competing counterions on Im solubility and on interconversions in solid phase. Hence, such factors must be taken into account during formulation optimization in drug research.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022",
title = "The influence of competing counterions on the solubility of imipramine",
pages = "27",
url = "https://hdl.handle.net/21.15107/rcub_cer_5396"
}

Marković, O. S., Gajić, B. P., Pešić, M. P.,& Verbić, T. Ž.. (2022). The influence of competing counterions on the solubility of imipramine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 27.
https://hdl.handle.net/21.15107/rcub_cer_5396

Marković OS, Gajić BP, Pešić MP, Verbić TŽ. The influence of competing counterions on the solubility of imipramine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:27.
https://hdl.handle.net/21.15107/rcub_cer_5396 .

Marković, Olivera S., Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana Ž., "The influence of competing counterions on the solubility of imipramine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):27,
https://hdl.handle.net/21.15107/rcub_cer_5396 .

TY  - CONF
AU  - Topalović, Igor A.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5397
AB  - Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
T1  - Investigation of clofazimine acid-base supersolubilization using various weak organic acids
SP  - 37
UR  - https://hdl.handle.net/21.15107/rcub_cer_5397
ER  - 

@conference{
author = "Topalović, Igor A. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "Nowadays, more than two-thirds of potential drugs currently being discovered are practically insoluble in water with solubility <100 μg/mL. Despite that, compounds with even lower solubility (<0.1 μg/mL) are commonly selected for further development which is very challenging, especially in the pharmaceutical formulation process1. Clofazimine (CFZ), an anti-leprosy drug with inhibitory activity against several coronaviruses, has a favourable safety profile2, but it is poorly soluble in aqueous media. Hence, it is important to develop a method for increasing its solubility. In this work, a relatively novel approach of enhancing solubility of weakly basic drugs by using weak acids that would not form salts with the drug (acid-base supersolubilization (ABS)) has been applied. CFZ aqueous solubility was determined in solutions of tartaric, citric, malic, malonic or maleic acid: in set I acid solutions had the same concentration (2.5 mol/L), and in the set II they were scaled to the same pH (1.0). The drug was added in stirred acid solution until a precipitate was noticed and, after filtration, CFZ concentration in samples was determined by HPLC. Based on set I, it was found that the solubility of CFZ had the highest value in the case of tartaric acid (0.46 mg/mL) compared to other acid solutions of the same concentration. In set II the highest CFZ concentration was determined in the malic acid solution which had the highest concentration (2.8 mol/L) among other acids. On contrary, maleic acid solution at pH=1.0 had the lowest molar concentration (0.5 mol/L) and therefore CFZ was minimally dissolved. Further research will be directed toward the examination of acid structure effect on CFZ solubility.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022",
title = "Investigation of clofazimine acid-base supersolubilization using various weak organic acids",
pages = "37",
url = "https://hdl.handle.net/21.15107/rcub_cer_5397"
}

Topalović, I. A., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). Investigation of clofazimine acid-base supersolubilization using various weak organic acids. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 37.
https://hdl.handle.net/21.15107/rcub_cer_5397

Topalović IA, Marković OS, Pešić MP, Verbić TŽ. Investigation of clofazimine acid-base supersolubilization using various weak organic acids. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:37.
https://hdl.handle.net/21.15107/rcub_cer_5397 .

Topalović, Igor A., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "Investigation of clofazimine acid-base supersolubilization using various weak organic acids" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):37,
https://hdl.handle.net/21.15107/rcub_cer_5397 .

TY  - CONF
AU  - Marjanović, Nemanja Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5401
AB  - In the modern drug research the number of practically insoluble potential drugs is increasing. Poor aqueous solubility can cause poor oral absorption and low bioavailability of drugs. Hence, solubility enhancement is considered as one of the most important challenges in the formulation and development of the dosage forms of drugs. Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis and leprosy. It is recently shown that CFZ has inhibitory activity against certain coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly lipophilic molecule with extremely low solubility, it is quite a challenge to find appropriate method for CFZ solubilization. The aim of this work was to investigate the effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method (pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures prepared without melting. Besides that, the IR spectra of these mixtures revealed that characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) probably due to CFZ-GA interactions. Preliminary results presented in this study illustrate that MSA and GA can be used for solubility improvement of CFZ.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
T1  - The effect of methanesulfonic and glutaric acids on the solubility of clofazimine
SP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cer_5401
ER  - 

@conference{
author = "Marjanović, Nemanja Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "In the modern drug research the number of practically insoluble potential drugs is increasing. Poor aqueous solubility can cause poor oral absorption and low bioavailability of drugs. Hence, solubility enhancement is considered as one of the most important challenges in the formulation and development of the dosage forms of drugs. Clofazimine (CFZ) is an antibiotic drug which is used in the treatment of tuberculosis and leprosy. It is recently shown that CFZ has inhibitory activity against certain coronaviruses and can antagonize the replication of SARS-CoV-2.1 Since CFZ is highly lipophilic molecule with extremely low solubility, it is quite a challenge to find appropriate method for CFZ solubilization. The aim of this work was to investigate the effect of methanesulfonic (MSA) and glutaric (GA) acids on the solubility of CFZ. The effect of MSA on the solubility of CFZ was studied by the pH-Ramp shake-flask method (pH-RSF).2 The solubility of CFZ was determined in the presence of GA in two ways: 1) by melting a mixture of CFZ and GA in different molar ratios, and then dissolving in water; 2) using the pH-RSF method. Interactions between CZ and GA were investigated by IR spectroscopy. It is shown that both MSA and GA increase the solubility of CFZ in acidic suspensions prepared by pH-RSF method. Also, solubility enhancement was observed in the molten CFZ-GA mixtures (molar ratio 1:1 and 1:4) compared to mixtures prepared without melting. Besides that, the IR spectra of these mixtures revealed that characteristic CFZ band was shifted in molted CFZ-GA mixture (molar ratio 1:1) probably due to CFZ-GA interactions. Preliminary results presented in this study illustrate that MSA and GA can be used for solubility improvement of CFZ.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022",
title = "The effect of methanesulfonic and glutaric acids on the solubility of clofazimine",
pages = "40",
url = "https://hdl.handle.net/21.15107/rcub_cer_5401"
}

Marjanović, N. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). The effect of methanesulfonic and glutaric acids on the solubility of clofazimine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 40.
https://hdl.handle.net/21.15107/rcub_cer_5401

Marjanović NŽ, Marković OS, Pešić MP, Verbić TŽ. The effect of methanesulfonic and glutaric acids on the solubility of clofazimine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:40.
https://hdl.handle.net/21.15107/rcub_cer_5401 .

Marjanović, Nemanja Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "The effect of methanesulfonic and glutaric acids on the solubility of clofazimine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):40,
https://hdl.handle.net/21.15107/rcub_cer_5401 .

TY  - CONF
AU  - Mrđinac, Jelena Ž.
AU  - Marković, Olivera S.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5398
AB  - The ionization constant (usually expressed in logarithmic form, pKa) is important physicochemical parameter which is used to characterize the acid-base chemistry of a compound. Since most drugs contain one or more ionizable functional groups, knowledge of pKa values is necessary in drug research. The most common techniques used for pKa determination are potentiometry and spectrophotometry. Potentiometry is a method of choice when ionization processes are overlapping, as in such case it is not possible to obtain the absorption spectrum of each species present in solution. The aim of this work was the comparative analysis of pKa determination using potentiometry and spectrophotometry for model compounds with overlapping ionization processes: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric titrations were performed with pSOL Model 3 instrument (pION) equipped with pS software package for titration data analysis.1 Avdeef–Bucher four–parameter equation was used for electrode standardization.2 To overcome the above-mentioned limitation of spectrophotometry, the alternative approach was applied in this study. The new aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was used for the solutions preparation of the model compounds in pH range 1 – 12. This buffer has numerous advantages like UV-transparency, resistance to pH changes upon standing for several days, useful buffer capacity and constant ionic strength in the wide range of pH values. Absorption spectra were recorded according to specific procedure which was carefully designed to avoid systematic errors. Collected absorption spectra will be used for the development of the algorithm for the spectral deconvolution (using MATLAB). Such software can be very useful tool in the drug research, especially for the analysis of the compounds which pKa values cannot be determined by potentiometry.
PB  - Belgrade : Serbian Chemical Society
PB  - Belgrade : Serbian Young Chemists’ Club
C3  - Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
T1  - Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_cer_5398
ER  - 

@conference{
author = "Mrđinac, Jelena Ž. and Marković, Olivera S. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "The ionization constant (usually expressed in logarithmic form, pKa) is important physicochemical parameter which is used to characterize the acid-base chemistry of a compound. Since most drugs contain one or more ionizable functional groups, knowledge of pKa values is necessary in drug research. The most common techniques used for pKa determination are potentiometry and spectrophotometry. Potentiometry is a method of choice when ionization processes are overlapping, as in such case it is not possible to obtain the absorption spectrum of each species present in solution. The aim of this work was the comparative analysis of pKa determination using potentiometry and spectrophotometry for model compounds with overlapping ionization processes: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. The potentiometric titrations were performed with pSOL Model 3 instrument (pION) equipped with pS software package for titration data analysis.1 Avdeef–Bucher four–parameter equation was used for electrode standardization.2 To overcome the above-mentioned limitation of spectrophotometry, the alternative approach was applied in this study. The new aminocaproate phosphate buffer (containing phosphoric and ε-aminocaproic acids) was used for the solutions preparation of the model compounds in pH range 1 – 12. This buffer has numerous advantages like UV-transparency, resistance to pH changes upon standing for several days, useful buffer capacity and constant ionic strength in the wide range of pH values. Absorption spectra were recorded according to specific procedure which was carefully designed to avoid systematic errors. Collected absorption spectra will be used for the development of the algorithm for the spectral deconvolution (using MATLAB). Such software can be very useful tool in the drug research, especially for the analysis of the compounds which pKa values cannot be determined by potentiometry.",
publisher = "Belgrade : Serbian Chemical Society, Belgrade : Serbian Young Chemists’ Club",
journal = "Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022",
title = "Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine",
pages = "42",
url = "https://hdl.handle.net/21.15107/rcub_cer_5398"
}

Mrđinac, J. Ž., Marković, O. S., Pešić, M. P.,& Verbić, T. Ž.. (2022). Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022
Belgrade : Serbian Chemical Society., 42.
https://hdl.handle.net/21.15107/rcub_cer_5398

Mrđinac JŽ, Marković OS, Pešić MP, Verbić TŽ. Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine. in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022. 2022;:42.
https://hdl.handle.net/21.15107/rcub_cer_5398 .

Mrđinac, Jelena Ž., Marković, Olivera S., Pešić, Miloš P., Verbić, Tatjana Ž., "Comparative analysis of ionization constants determination using spectrophotometry and potentiometry: 3-aminobenzoic acid, 1,3,5-benzenetricarboxylic acid and tyrosine" in Book of Abstracts - 8th Conference of Young Chemists of Serbia, Belgrade, Serbia, 29th October, 2022 (2022):42,
https://hdl.handle.net/21.15107/rcub_cer_5398 .

TY  - CONF
AU  - Marković, Olivera
AU  - Gajić, Brankica P.
AU  - Pešić, Miloš P.
AU  - Verbić, Tatjana Ž.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5087
AB  - Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom. Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5 5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova.
AB  - The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self-aggregation – pentamer formation (Am5H5 5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.
PB  - Belgrade : Serbian Chemical Society
C3  - Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine
T1  - Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina
T1  - Study of equilibria in heterogeneous systems of tricyclic  antidepressant amitriptyline
SP  - 53
EP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_cer_5087
ER  - 

@conference{
author = "Marković, Olivera and Gajić, Brankica P. and Pešić, Miloš P. and Verbić, Tatjana Ž.",
year = "2022",
abstract = "Cilj ovog rada bio je proučavanje ravnoteža u heterogenim sistemima tricikličnog 
antidepresiva amitriptilina (Am) koji sadrže hloride i/ili fosfate. Rastvorljivost Am u 
uslovima povećane jonske sile određena je pH–Ramp shake–flask metodom. Veća 
rastvorljivost Am u kiseloj sredini od očekivane, posledica je agregacije – analiza 
eksperimentalnih podataka pomoću programa pDISOL–XTM ukazuje na verovatno 
građenje pentamera Am5H5 5+. Kritična micelarna koncentracija i stepen disocijacije 
agregata određeni su primenom konduktometrijskih titracija. U baznoj sredini primećena je 
delimična degradacija Am. Eksperimentalno dobijeni podaci o rastvorljivosti biološki 
aktivnih supstanci i postojećim ravnotežama u heterogenim sistemima važni su u svim 
fazama dizajna i razvoja lekova., The aim of this work was to study the equilibria in tricyclic antidepressant amitriptyline 
(Am) heterogeneous systems containing chloride and/or phosphate ions. Solubility of Am 
in high ionic strength conditions was determined using pH–Ramp shake–flask method.1, 2
Higher solubility of Am than expected in an acidic media is a consequence of self-aggregation – pentamer formation (Am5H5 5+) according to pDISOL–XTM analysis. Critical 
micelle concentration and the degree of the aggregate dissociation were determined by 
conductometric titrations. Partial degradation of Am in alkaline suspensions was observed. 
Experimental studies of solubility as well as the existing equilibria in heterogeneous 
systems of biologically active compounds are important at all stages of drug design and 
development.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine",
title = "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina, Study of equilibria in heterogeneous systems of tricyclic  antidepressant amitriptyline",
pages = "53-53",
url = "https://hdl.handle.net/21.15107/rcub_cer_5087"
}

Marković, O., Gajić, B. P., Pešić, M. P.,& Verbić, T. Ž.. (2022). Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine
Belgrade : Serbian Chemical Society., 53-53.
https://hdl.handle.net/21.15107/rcub_cer_5087

Marković O, Gajić BP, Pešić MP, Verbić TŽ. Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina. in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine. 2022;:53-53.
https://hdl.handle.net/21.15107/rcub_cer_5087 .

Marković, Olivera, Gajić, Brankica P., Pešić, Miloš P., Verbić, Tatjana Ž., "Proučavanje ravnoteža u heterogenim sistemima tricikličnog  antidepresiva amitriptilina" in Book of Abstracts, Proceedings - 58th Meeting of the Serbian Chemical Society, Belgrade, Serbia, June 9-10, 2022 / Kratki izvodi radova, kjniga radova - 58. Savetovanje Srpskog hemijskog društva, Beograd 9. i 10. jun 2022. godine (2022):53-53,
https://hdl.handle.net/21.15107/rcub_cer_5087 .

TY  - JOUR
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4934
AB  - The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
VL  - 19
IS  - 2
SP  - 710
EP  - 719
DO  - 10.1021/acs.molpharmaceut.1c00919
ER  - 

@article{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints",
volume = "19",
number = "2",
pages = "710-719",
doi = "10.1021/acs.molpharmaceut.1c00919"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics
American Chemical Society (ACS)., 19(2), 710-719.
https://doi.org/10.1021/acs.molpharmaceut.1c00919

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics. 2022;19(2):710-719.
doi:10.1021/acs.molpharmaceut.1c00919 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints" in Molecular Pharmaceutics, 19, no. 2 (2022):710-719,
https://doi.org/10.1021/acs.molpharmaceut.1c00919 . .

TY  - DATA
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4935
AB  - Additional experimental details; preparation of stock suspensions for low-to-high pH and high-to-low pH titrations; titration and solubility data for titration sets 1–11; elemental analysis data from titration sets 9, 3, 6, and 7; and HPLC UV/VIS analysis─sample chromatograms and calibration diagram
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"
DO  - 10.1021/acs.molpharmaceut.1c00919.s001
ER  - 

@misc{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "Additional experimental details; preparation of stock suspensions for low-to-high pH and high-to-low pH titrations; titration and solubility data for titration sets 1–11; elemental analysis data from titration sets 9, 3, 6, and 7; and HPLC UV/VIS analysis─sample chromatograms and calibration diagram",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"",
doi = "10.1021/acs.molpharmaceut.1c00919.s001"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints". in Molecular Pharmaceutics
American Chemical Society (ACS)..
https://doi.org/10.1021/acs.molpharmaceut.1c00919.s001

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints". in Molecular Pharmaceutics. 2022;.
doi:10.1021/acs.molpharmaceut.1c00919.s001 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"" in Molecular Pharmaceutics (2022),
https://doi.org/10.1021/acs.molpharmaceut.1c00919.s001 . .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Verbić, Tatjana
AU  - Marković, Olivera
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
AU  - Matijević, Borko
PY  - 2021
UR  - http://savremenimaterijali.info/
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4361
AB  - Carbohydrazone derivatives represent a very significant
class of compounds due to their wide biological activity. Ionization states of
functional groups present in the molecule are of vital importance for understanding
of the pharmacokinetic and pharmacodynamic properties of the
newly synthesized compounds. One of the physicochemical parameters, the
ionization constant (pKa), can be used as a molecular descriptor in order to relate
structure and activity of a compound, which may indicate further potential
application of newly synthesized derivatives. In this work, ionization
constants of thirteen monocarbohydrazone derivatives were determined using
potentiometric method, in order to obtain information about their ionization
states under certain conditions.
AB  - Деривати карбохидразона представљају веома значај-
на једињења за проучавање с обзиром да многа од њих показују веома
изражену биолошку активност. Познавање јонизационог стања функци-
оналних група присутних у молекулу је од виталног значаја за разумева-
ње фармакокинетичких и фармакодинамичких особина новосинтетиса-
них једињења. Један од важнијих физичко-хемијских параметара, кисе-
линска константа (pKa), може да послужи као молекулски дескриптор за
повезивање односа стуктуре и активности једињења, што може укази-
вати на даљу потенцијалну примену новосинтетисаних деривата. У
овом раду, применом потенциометријске методе, одређене су киселин-
ске константе за тринаест синтетисаних једињења из серије монокарбо-
хидразона у циљу добијања информација о њиховим јонизационим ста-
њима при одређеним условима.
PB  - Academy of Sciences and Arts of the Republic of Srpska / Академија наука и умјетности Републике Српске
C3  - 13th International Scientific Conference Contemporary Materials 2020, Proccedings,  Banja Luka, 11.09.2020.
T1  - Determination of ionization constants of selected monocarbohydrazone derivatives
T1  - Одређивање јонизационих константи одабраних деривата монокарбохидразона
SP  - 415
EP  - 422
UR  - https://hdl.handle.net/21.15107/rcub_cer_4361
ER  - 

@conference{
author = "Mrđan, Gorana and Verbić, Tatjana and Marković, Olivera and Vaštag, Đenđi and Apostolov, Suzana and Matijević, Borko",
year = "2021",
abstract = "Carbohydrazone derivatives represent a very significant
class of compounds due to their wide biological activity. Ionization states of
functional groups present in the molecule are of vital importance for understanding
of the pharmacokinetic and pharmacodynamic properties of the
newly synthesized compounds. One of the physicochemical parameters, the
ionization constant (pKa), can be used as a molecular descriptor in order to relate
structure and activity of a compound, which may indicate further potential
application of newly synthesized derivatives. In this work, ionization
constants of thirteen monocarbohydrazone derivatives were determined using
potentiometric method, in order to obtain information about their ionization
states under certain conditions., Деривати карбохидразона представљају веома значај-
на једињења за проучавање с обзиром да многа од њих показују веома
изражену биолошку активност. Познавање јонизационог стања функци-
оналних група присутних у молекулу је од виталног значаја за разумева-
ње фармакокинетичких и фармакодинамичких особина новосинтетиса-
них једињења. Један од важнијих физичко-хемијских параметара, кисе-
линска константа (pKa), може да послужи као молекулски дескриптор за
повезивање односа стуктуре и активности једињења, што може укази-
вати на даљу потенцијалну примену новосинтетисаних деривата. У
овом раду, применом потенциометријске методе, одређене су киселин-
ске константе за тринаест синтетисаних једињења из серије монокарбо-
хидразона у циљу добијања информација о њиховим јонизационим ста-
њима при одређеним условима.",
publisher = "Academy of Sciences and Arts of the Republic of Srpska / Академија наука и умјетности Републике Српске",
journal = "13th International Scientific Conference Contemporary Materials 2020, Proccedings,  Banja Luka, 11.09.2020.",
title = "Determination of ionization constants of selected monocarbohydrazone derivatives, Одређивање јонизационих константи одабраних деривата монокарбохидразона",
pages = "415-422",
url = "https://hdl.handle.net/21.15107/rcub_cer_4361"
}

Mrđan, G., Verbić, T., Marković, O., Vaštag, Đ., Apostolov, S.,& Matijević, B.. (2021). Determination of ionization constants of selected monocarbohydrazone derivatives. in 13th International Scientific Conference Contemporary Materials 2020, Proccedings,  Banja Luka, 11.09.2020.
Academy of Sciences and Arts of the Republic of Srpska / Академија наука и умјетности Републике Српске., 415-422.
https://hdl.handle.net/21.15107/rcub_cer_4361

Mrđan G, Verbić T, Marković O, Vaštag Đ, Apostolov S, Matijević B. Determination of ionization constants of selected monocarbohydrazone derivatives. in 13th International Scientific Conference Contemporary Materials 2020, Proccedings,  Banja Luka, 11.09.2020.. 2021;:415-422.
https://hdl.handle.net/21.15107/rcub_cer_4361 .

Mrđan, Gorana, Verbić, Tatjana, Marković, Olivera, Vaštag, Đenđi, Apostolov, Suzana, Matijević, Borko, "Determination of ionization constants of selected monocarbohydrazone derivatives" in 13th International Scientific Conference Contemporary Materials 2020, Proccedings,  Banja Luka, 11.09.2020. (2021):415-422,
https://hdl.handle.net/21.15107/rcub_cer_4361 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
AU  - Rašeta, Milena
AU  - Verbić, Tatjana
AU  - Marković, Olivera
AU  - Matijević, Borko
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4760
AB  - Carbohydrazones and their thio analogs represent compounds obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl compounds. Due to their structure, relatively simple synthesis, and high reactivity, mentioned derivatives have a wide range of applications in all fields. In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method. Also, the influence of specific 
and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption spectra was investigated and quantified using the linear solvation energy relationships method and Catalan’s model. Finally, by applying the DPPH assay, the antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone derivatives proved to be significantly more active when compared to carbohydrazones.
C3  - Programme and the book of abstracts, 14th International Scientific Conference Contemporary Materials 2021
T1  - Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives
SP  - 40
EP  - 40
UR  - https://hdl.handle.net/21.15107/rcub_cer_4760
ER  - 

@conference{
author = "Mrđan, Gorana and Vaštag, Đenđi and Apostolov, Suzana and Rašeta, Milena and Verbić, Tatjana and Marković, Olivera and Matijević, Borko",
year = "2021",
abstract = "Carbohydrazones and their thio analogs represent compounds obtained by condensation of carbohydrazide and thiocarbohydrazide with carbonyl compounds. Due to their structure, relatively simple synthesis, and high reactivity, mentioned derivatives have a wide range of applications in all fields. In this study, ionization constants of four newly synthesized mono(thio)carbohydrazones were determined by applying the potentiometric method. Also, the influence of specific 
and nonspecific intermolecular interactions on maxima shifting in UV-Vis absorption spectra was investigated and quantified using the linear solvation energy relationships method and Catalan’s model. Finally, by applying the DPPH assay, the antioxidant potential of the newly synthesized compounds was determined, and thiocarbohydrazone derivatives proved to be significantly more active when compared to carbohydrazones.",
journal = "Programme and the book of abstracts, 14th International Scientific Conference Contemporary Materials 2021",
title = "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives",
pages = "40-40",
url = "https://hdl.handle.net/21.15107/rcub_cer_4760"
}

Mrđan, G., Vaštag, Đ., Apostolov, S., Rašeta, M., Verbić, T., Marković, O.,& Matijević, B.. (2021). Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in Programme and the book of abstracts, 14th International Scientific Conference Contemporary Materials 2021, 40-40.
https://hdl.handle.net/21.15107/rcub_cer_4760

Mrđan G, Vaštag Đ, Apostolov S, Rašeta M, Verbić T, Marković O, Matijević B. Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives. in Programme and the book of abstracts, 14th International Scientific Conference Contemporary Materials 2021. 2021;:40-40.
https://hdl.handle.net/21.15107/rcub_cer_4760 .

Mrđan, Gorana, Vaštag, Đenđi, Apostolov, Suzana, Rašeta, Milena, Verbić, Tatjana, Marković, Olivera, Matijević, Borko, "Investigation of physicochemical properties and potential biological activity of 2-pyridine-(thio)carbohydrazone derivatives" in Programme and the book of abstracts, 14th International Scientific Conference Contemporary Materials 2021 (2021):40-40,
https://hdl.handle.net/21.15107/rcub_cer_4760 .

TY  - JOUR
AU  - Mrđan, Gorana S.
AU  - Vastag, Gyöngyi Gy.
AU  - Škorić, Dušan
AU  - Radanović, Mirjana M.
AU  - Verbić, Tatjana
AU  - Milčić, Miloš
AU  - Stojiljković, Ivana N.
AU  - Marković, Olivera
AU  - Matijević, Borko
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4055
AB  - Derivatives of thiocarbohydrazone studied so far have shown great biological activity such as antioxidant, antimicrobial, and
anticancer.Most of these compounds are bis-substituted derivatives,while monothiocarbohydrazones are much less investigated.
Еighteen monothiocarbohydrazones were synthesized and subjected to physicochemical characterization in order to facilitate the
examination of their potential biological activity and application in future studies. The structure of synthesized derivatives was
confirmed with NMR and FT–IR spectroscopy, and with elemental analysis. For one of the compounds, single-crystal X-ray
diffraction analysis was performed. Specific and non-specific molecular interactions were interpreted by LSER principles, using
Catalan’s model. For additional information about the dominance and influence of the interactions presented, correlations with
Hansen’s solubility parameters were calculated. Influence of the type and position of the substituent on absorption maxima was
determined with LFER (linear free-energy relationship) principles, using Hammett’s equation. Acidity constants of the synthesized
compounds were theoretically calculated and experimentally determined. Moreover, the excitation of a molecule by a
photon of UV–Vis light was interpreted by time-dependent density functional theory (TD–DFT) calculations of UV absorption
bands, and intramolecular charge transfer (ICT) was quantified by calculations of the charge transfer distances (DCT).
PB  - Springer
T2  - Structural Chemistry
T1  - Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives
DO  - 10.1007/s11224-020-01700-y
ER  - 

@article{
author = "Mrđan, Gorana S. and Vastag, Gyöngyi Gy. and Škorić, Dušan and Radanović, Mirjana M. and Verbić, Tatjana and Milčić, Miloš and Stojiljković, Ivana N. and Marković, Olivera and Matijević, Borko",
year = "2021",
abstract = "Derivatives of thiocarbohydrazone studied so far have shown great biological activity such as antioxidant, antimicrobial, and
anticancer.Most of these compounds are bis-substituted derivatives,while monothiocarbohydrazones are much less investigated.
Еighteen monothiocarbohydrazones were synthesized and subjected to physicochemical characterization in order to facilitate the
examination of their potential biological activity and application in future studies. The structure of synthesized derivatives was
confirmed with NMR and FT–IR spectroscopy, and with elemental analysis. For one of the compounds, single-crystal X-ray
diffraction analysis was performed. Specific and non-specific molecular interactions were interpreted by LSER principles, using
Catalan’s model. For additional information about the dominance and influence of the interactions presented, correlations with
Hansen’s solubility parameters were calculated. Influence of the type and position of the substituent on absorption maxima was
determined with LFER (linear free-energy relationship) principles, using Hammett’s equation. Acidity constants of the synthesized
compounds were theoretically calculated and experimentally determined. Moreover, the excitation of a molecule by a
photon of UV–Vis light was interpreted by time-dependent density functional theory (TD–DFT) calculations of UV absorption
bands, and intramolecular charge transfer (ICT) was quantified by calculations of the charge transfer distances (DCT).",
publisher = "Springer",
journal = "Structural Chemistry",
title = "Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives",
doi = "10.1007/s11224-020-01700-y"
}

Mrđan, G. S., Vastag, G. Gy., Škorić, D., Radanović, M. M., Verbić, T., Milčić, M., Stojiljković, I. N., Marković, O.,& Matijević, B.. (2021). Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives. in Structural Chemistry
Springer..
https://doi.org/10.1007/s11224-020-01700-y

Mrđan GS, Vastag GG, Škorić D, Radanović MM, Verbić T, Milčić M, Stojiljković IN, Marković O, Matijević B. Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives. in Structural Chemistry. 2021;.
doi:10.1007/s11224-020-01700-y .

Mrđan, Gorana S., Vastag, Gyöngyi Gy., Škorić, Dušan, Radanović, Mirjana M., Verbić, Tatjana, Milčić, Miloš, Stojiljković, Ivana N., Marković, Olivera, Matijević, Borko, "Synthesis, physicochemical characterization, and TD–DFT calculations of monothiocarbohydrazone derivatives" in Structural Chemistry (2021),
https://doi.org/10.1007/s11224-020-01700-y . .

TY  - CONF
AU  - Marković, Olivera
AU  - Marjanović, Nemanja Ž.
AU  - Patel, Nirali
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4730
AB  - Solubility is important physicochemical parameter and determines drug stability, bioavailability and 
therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in 
a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine 
hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, 
differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid 
precipitate analysis.
AB  - Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki 
aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog 
rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, 
prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim 
preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i 
sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija
čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije 
i difrakcije X-zraka.
PB  - Belgrade : Serbian Chemical Society
C3  - Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva
T1  - pH-Dependent solubility profile of nortriptyline hydrochloride
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_cer_4730
ER  - 

@conference{
author = "Marković, Olivera and Marjanović, Nemanja Ž. and Patel, Nirali and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2021",
abstract = "Solubility is important physicochemical parameter and determines drug stability, bioavailability and 
therapeutic action. The aim of this study was to examine solubility of nortriptyline hydrochloride in 
a wide pH range, using pH-Ramp Shake-Flask method, already applied to desipramine 
hydrochloride [1] and based of recently published recommendations [2]. Solubility was measured in phosphate buffer, in chloride-free media and phoshate-free media, using both nortriptyline base and nortriptyline hydrochloride as starting material. Elemental analysis, termogravimetric analysis, 
differential scaning calorimetric analysis and powder X-ray diffraction analysis were used for solid 
precipitate analysis., Rastvorljivost je značajno fizičko-hemijsko svojstvo biološki aktivnih i potencijalno biološki 
aktivnih supstancija, koje određuje stabilnost, biodostupnost i terapeutsko dejstvo leka. Cilj ovog 
rada je ispitivanje rastvorljivosti nortriptilin-hidrohlorida, pomoću pH-Ramp Shake-Flask metode, 
prethodno primenjene na desipramin-hidrohlorid [1]. Eksperimenti su izvedeni prema novim 
preporukama iz literature [2]. Rastvorljivost je određena u fosfatnom puferu, u sistemu bez hlorida i 
sistemu bez fosfata, koristeći nortriptilin bazu i nortriptilin-hidrohlorid. Urađena je i katakterizacija
čvrste faze pomoću elementalne analize, termogravimetrije, diferencijalne skenirajuće kalorimetrije 
i difrakcije X-zraka.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva",
title = "pH-Dependent solubility profile of nortriptyline hydrochloride",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_cer_4730"
}

Marković, O., Marjanović, N. Ž., Patel, N., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2021). pH-Dependent solubility profile of nortriptyline hydrochloride. in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva
Belgrade : Serbian Chemical Society., 32-32.
https://hdl.handle.net/21.15107/rcub_cer_4730

Marković O, Marjanović NŽ, Patel N, Serajuddin ATM, Avdeef A, Verbić T. pH-Dependent solubility profile of nortriptyline hydrochloride. in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva. 2021;:32-32.
https://hdl.handle.net/21.15107/rcub_cer_4730 .

Marković, Olivera, Marjanović, Nemanja Ž., Patel, Nirali, Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profile of nortriptyline hydrochloride" in Book of abstracts / Proceedings 57th Meeting of the Serbian Chemical Society // Kratki izvodi radova / Knjiga radova 57. Savetovanje Srpskog hemijskog društva (2021):32-32,
https://hdl.handle.net/21.15107/rcub_cer_4730 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Verbić, Tatjana
AU  - Marković, Olivera
AU  - Matijević, Borko
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
PY  - 2020
UR  - http://savremenimaterijali.info/
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3688
AB  - Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized compounds. One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a compound, which may indicate further potential application of newly synthesized derivatives. In this work, ionization constants of twenty monocarbohydrazone derivatives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.
PB  - Academy of Sciences and Arts of the Republic of Srpska
C3  - 13th International Scientific Conference Contemporary Materials 2020, Programme and the Book of Abstracts, 11.09.2020.
T1  - Determination of ionization constants of selected monocarbohydrazone derivatives
SP  - 50
EP  - 50
UR  - https://hdl.handle.net/21.15107/rcub_cer_3688
ER  - 

@conference{
author = "Mrđan, Gorana and Verbić, Tatjana and Marković, Olivera and Matijević, Borko and Vaštag, Đenđi and Apostolov, Suzana",
year = "2020",
abstract = "Carbohydrazone derivatives represent a very significant class of compounds due to their wide biological activity. Ionization states of functional groups present in the molecule are of vital importance for understanding of the pharmacokinetic and pharmacodynamic properties of the newly synthesized compounds. One of the physicochemical parameters, the ionization constant (pKa), can be used as a molecular descriptor in order to relate structure and activity of a compound, which may indicate further potential application of newly synthesized derivatives. In this work, ionization constants of twenty monocarbohydrazone derivatives were determined using potentiometric method, in order to obtain information about their ionization states under certain conditions.",
publisher = "Academy of Sciences and Arts of the Republic of Srpska",
journal = "13th International Scientific Conference Contemporary Materials 2020, Programme and the Book of Abstracts, 11.09.2020.",
title = "Determination of ionization constants of selected monocarbohydrazone derivatives",
pages = "50-50",
url = "https://hdl.handle.net/21.15107/rcub_cer_3688"
}

Mrđan, G., Verbić, T., Marković, O., Matijević, B., Vaštag, Đ.,& Apostolov, S.. (2020). Determination of ionization constants of selected monocarbohydrazone derivatives. in 13th International Scientific Conference Contemporary Materials 2020, Programme and the Book of Abstracts, 11.09.2020.
Academy of Sciences and Arts of the Republic of Srpska., 50-50.
https://hdl.handle.net/21.15107/rcub_cer_3688

Mrđan G, Verbić T, Marković O, Matijević B, Vaštag Đ, Apostolov S. Determination of ionization constants of selected monocarbohydrazone derivatives. in 13th International Scientific Conference Contemporary Materials 2020, Programme and the Book of Abstracts, 11.09.2020.. 2020;:50-50.
https://hdl.handle.net/21.15107/rcub_cer_3688 .

Mrđan, Gorana, Verbić, Tatjana, Marković, Olivera, Matijević, Borko, Vaštag, Đenđi, Apostolov, Suzana, "Determination of ionization constants of selected monocarbohydrazone derivatives" in 13th International Scientific Conference Contemporary Materials 2020, Programme and the Book of Abstracts, 11.09.2020. (2020):50-50,
https://hdl.handle.net/21.15107/rcub_cer_3688 .

TY  - CONF
AU  - Mrđan, Gorana
AU  - Verbić, Tatjana
AU  - Marković, Olivera
AU  - Matijević, Borko
AU  - Vaštag, Đenđi
AU  - Apostolov, Suzana
PY  - 2020
UR  - http://savremenimaterijali.info/
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3689
AB  - Poster presented at: 13th International Scientific Conference Contemporary Materials 2020, Banja Luka, 11th September, 2020
T1  - Determination of ionization constants of selected monocarbohydrazone derivatites
UR  - https://hdl.handle.net/21.15107/rcub_cer_3689
ER  - 

@conference{
author = "Mrđan, Gorana and Verbić, Tatjana and Marković, Olivera and Matijević, Borko and Vaštag, Đenđi and Apostolov, Suzana",
year = "2020",
abstract = "Poster presented at: 13th International Scientific Conference Contemporary Materials 2020, Banja Luka, 11th September, 2020",
title = "Determination of ionization constants of selected monocarbohydrazone derivatites",
url = "https://hdl.handle.net/21.15107/rcub_cer_3689"
}

Mrđan, G., Verbić, T., Marković, O., Matijević, B., Vaštag, Đ.,& Apostolov, S.. (2020). Determination of ionization constants of selected monocarbohydrazone derivatites. .
https://hdl.handle.net/21.15107/rcub_cer_3689

Mrđan G, Verbić T, Marković O, Matijević B, Vaštag Đ, Apostolov S. Determination of ionization constants of selected monocarbohydrazone derivatites. 2020;.
https://hdl.handle.net/21.15107/rcub_cer_3689 .

Mrđan, Gorana, Verbić, Tatjana, Marković, Olivera, Matijević, Borko, Vaštag, Đenđi, Apostolov, Suzana, "Determination of ionization constants of selected monocarbohydrazone derivatites" (2020),
https://hdl.handle.net/21.15107/rcub_cer_3689 .

TY  - JOUR
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3211
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .

TY  - JOUR
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Verbić, Tatjana
AU  - Avdeef, Alex
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3342
AB  - Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates
VL  - 133
SP  - 264
EP  - 274
DO  - 10.1016/j.ejps.2019.03.014
ER  - 

@article{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Verbić, Tatjana and Avdeef, Alex",
year = "2019",
abstract = "Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates",
volume = "133",
pages = "264-274",
doi = "10.1016/j.ejps.2019.03.014"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Verbić, T.,& Avdeef, A.. (2019). Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences
Elsevier., 133, 264-274.
https://doi.org/10.1016/j.ejps.2019.03.014

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Verbić T, Avdeef A. Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates. in European Journal of Pharmaceutical Sciences. 2019;133:264-274.
doi:10.1016/j.ejps.2019.03.014 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Verbić, Tatjana, Avdeef, Alex, "Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates" in European Journal of Pharmaceutical Sciences, 133 (2019):264-274,
https://doi.org/10.1016/j.ejps.2019.03.014 . .

TY  - CONF
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3404
AB  - The aim of this study was to examine solubility-pH behavior of desipramine structural analogues:
imipramine and amitriptyline hydrochlorides. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult,
especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis
detection. Different techniques were used for solid phase characterization. Solid phase
characterization is particularly important in complicated systems like this.
PB  - International Association of Physical Chemists
C3  - 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
T1  - pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides
SP  - 51
EP  - 51
UR  - https://hdl.handle.net/21.15107/rcub_cer_3404
ER  - 

@conference{
author = "Marković, Olivera and Pešić, Miloš P. and Avdeef, Alex and Verbić, Tatjana",
year = "2019",
abstract = "The aim of this study was to examine solubility-pH behavior of desipramine structural analogues:
imipramine and amitriptyline hydrochlorides. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult,
especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis
detection. Different techniques were used for solid phase characterization. Solid phase
characterization is particularly important in complicated systems like this.",
publisher = "International Association of Physical Chemists",
journal = "8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts",
title = "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides",
pages = "51-51",
url = "https://hdl.handle.net/21.15107/rcub_cer_3404"
}

Marković, O., Pešić, M. P., Avdeef, A.,& Verbić, T.. (2019). pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
International Association of Physical Chemists., 51-51.
https://hdl.handle.net/21.15107/rcub_cer_3404

Marković O, Pešić MP, Avdeef A, Verbić T. pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts. 2019;:51-51.
https://hdl.handle.net/21.15107/rcub_cer_3404 .

Marković, Olivera, Pešić, Miloš P., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides" in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts (2019):51-51,
https://hdl.handle.net/21.15107/rcub_cer_3404 .

TY  - CONF
AU  - Marković, Olivera
AU  - Pešić, Miloš P.
AU  - Shah, Ankita V.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3405
AB  - The solution behavior of desipramine hydrochloride (DsHCl) in phosphate-buffered and unbuffered solutions is evidently complicated and only tentatively understood. The computer program pDISOL-X was used to design the structured pH-ramp shake flask experiments (pHRSF method), to process the data, and to refine the equilibrium constants.
PB  - International Association of Physical Chemists
C3  - 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
T1  - Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates
SP  - 17
EP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_cer_3405
ER  - 

@conference{
author = "Marković, Olivera and Pešić, Miloš P. and Shah, Ankita V. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2019",
abstract = "The solution behavior of desipramine hydrochloride (DsHCl) in phosphate-buffered and unbuffered solutions is evidently complicated and only tentatively understood. The computer program pDISOL-X was used to design the structured pH-ramp shake flask experiments (pHRSF method), to process the data, and to refine the equilibrium constants.",
publisher = "International Association of Physical Chemists",
journal = "8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts",
title = "Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates",
pages = "17-17",
url = "https://hdl.handle.net/21.15107/rcub_cer_3405"
}

Marković, O., Pešić, M. P., Shah, A. V., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2019). Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts
International Association of Physical Chemists., 17-17.
https://hdl.handle.net/21.15107/rcub_cer_3405

Marković O, Pešić MP, Shah AV, Serajuddin ATM, Avdeef A, Verbić T. Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates. in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts. 2019;:17-17.
https://hdl.handle.net/21.15107/rcub_cer_3405 .

Marković, Olivera, Pešić, Miloš P., Shah, Ankita V., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Desipramine solubility studies: enhanced solubility due to drug-buffer aggregates" in 8th World Conference on Physico-Chemical Methods in Drug Discovery, Split, Croatia, September 9-11, 2019 - Book of Abstracts (2019):17-17,
https://hdl.handle.net/21.15107/rcub_cer_3405 .

TY  - JOUR
AU  - Konstantinović, Jelena M.
AU  - Kiris, Erkan
AU  - Kota, Krishna P.
AU  - Kugelman-Tonos, Johanny
AU  - Videnović, Milica
AU  - Cazares, Lisa H.
AU  - Terzić-Jovanović, Nataša
AU  - Verbić, Tatjana
AU  - Anđelković, Boban D.
AU  - Duplantier, Allen J.
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2325
AB  - The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model
VL  - 61
IS  - 4
SP  - 1595
EP  - 1608
DO  - 10.1021/acs.jmedchem.7b01710
ER  - 

@article{
author = "Konstantinović, Jelena M. and Kiris, Erkan and Kota, Krishna P. and Kugelman-Tonos, Johanny and Videnović, Milica and Cazares, Lisa H. and Terzić-Jovanović, Nataša and Verbić, Tatjana and Anđelković, Boban D. and Duplantier, Allen J. and Bavari, Sina and Šolaja, Bogdan",
year = "2018",
abstract = "The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication. This appears to be the first example of LC inhibitors antagonizing BoNT intoxication in mouse embryonic stem cell derived motor neurons (mES-MNs) in a postexposure model. Oral administration of 16 was well tolerated in the mouse up to 600 mg/kg, q.d. Although adequate unbound drug levels were not achieved at this dose, the favorable in vitro ADMET results strongly support further work in this series.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model",
volume = "61",
number = "4",
pages = "1595-1608",
doi = "10.1021/acs.jmedchem.7b01710"
}

Konstantinović, J. M., Kiris, E., Kota, K. P., Kugelman-Tonos, J., Videnović, M., Cazares, L. H., Terzić-Jovanović, N., Verbić, T., Anđelković, B. D., Duplantier, A. J., Bavari, S.,& Šolaja, B.. (2018). New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 61(4), 1595-1608.
https://doi.org/10.1021/acs.jmedchem.7b01710

Konstantinović JM, Kiris E, Kota KP, Kugelman-Tonos J, Videnović M, Cazares LH, Terzić-Jovanović N, Verbić T, Anđelković BD, Duplantier AJ, Bavari S, Šolaja B. New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model. in Journal of Medicinal Chemistry. 2018;61(4):1595-1608.
doi:10.1021/acs.jmedchem.7b01710 .

Konstantinović, Jelena M., Kiris, Erkan, Kota, Krishna P., Kugelman-Tonos, Johanny, Videnović, Milica, Cazares, Lisa H., Terzić-Jovanović, Nataša, Verbić, Tatjana, Anđelković, Boban D., Duplantier, Allen J., Bavari, Sina, Šolaja, Bogdan, "New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model" in Journal of Medicinal Chemistry, 61, no. 4 (2018):1595-1608,
https://doi.org/10.1021/acs.jmedchem.7b01710 . .

TY  - JOUR
AU  - Marković, Olivera
AU  - Cvijetić, Ilija
AU  - Zlatović, Mario
AU  - Opsenica, Igor
AU  - Konstantinović, Jelena M.
AU  - Terzić-Jovanović, Nataša
AU  - Šolaja, Bogdan
AU  - Verbić, Tatjana
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2472
AB  - Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy
T1  - Human serum albumin binding of certain antimalarials
VL  - 192
SP  - 128
EP  - 139
DO  - 10.1016/j.saa.2017.10.061
ER  - 

@article{
author = "Marković, Olivera and Cvijetić, Ilija and Zlatović, Mario and Opsenica, Igor and Konstantinović, Jelena M. and Terzić-Jovanović, Nataša and Šolaja, Bogdan and Verbić, Tatjana",
year = "2018",
abstract = "Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy",
title = "Human serum albumin binding of certain antimalarials",
volume = "192",
pages = "128-139",
doi = "10.1016/j.saa.2017.10.061"
}

Marković, O., Cvijetić, I., Zlatović, M., Opsenica, I., Konstantinović, J. M., Terzić-Jovanović, N., Šolaja, B.,& Verbić, T.. (2018). Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy
Oxford : Pergamon-Elsevier Science Ltd., 192, 128-139.
https://doi.org/10.1016/j.saa.2017.10.061

Marković O, Cvijetić I, Zlatović M, Opsenica I, Konstantinović JM, Terzić-Jovanović N, Šolaja B, Verbić T. Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy. 2018;192:128-139.
doi:10.1016/j.saa.2017.10.061 .

Marković, Olivera, Cvijetić, Ilija, Zlatović, Mario, Opsenica, Igor, Konstantinović, Jelena M., Terzić-Jovanović, Nataša, Šolaja, Bogdan, Verbić, Tatjana, "Human serum albumin binding of certain antimalarials" in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy, 192 (2018):128-139,
https://doi.org/10.1016/j.saa.2017.10.061 . .