TY  - JOUR
AU  - Matošević, Ana
AU  - Opsenica, Dejan
AU  - Spasić, Marta
AU  - Maraković, Nikola
AU  - Zandona, Antonio
AU  - Žunec, Suzana
AU  - Bartolić, Marija
AU  - Kovarik, Zrinka
AU  - Bosak, Anita
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7159
AB  - The most successful therapeutic strategy in the treatment of Alzheimer's disease (AD) is directed toward increasing levels of the neurotransmitter acetylcholine (ACh) by inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the enzymes responsible for its hydrolysis. In this paper, we extended our study on 4-aminoquinolines as human cholinesterase inhibitors on twenty-six new 4-aminoquinolines containing an n-octylamino spacer on C(4) and different substituents on the terminal amino group. We evaluated the potency of new derivatives to act as multi-targeted ligands by determining their inhibition potency towards human AChE and BChE, ability to chelate biometals Fe, Cu and Zn, ability to inhibit the action of β-secretase 1 (BACE1) and their antioxidant capacity. All of the tested derivatives were very potent inhibitors of human AChE and BChE with inhibition constants (Ki) ranging from 0.0023 to 1.6 μM. Most of the compounds were estimated to be able to cross the blood-brain barrier (BBB) by passive transport and were nontoxic to human neuronal, kidney and liver cells in concentrations in which they inhibit cholinesterases. Generally, newly synthesised compounds were weak reductants compared to standard antioxidants, but all possessed a certain amount of antioxidant activity compared to tacrine. Of the eleven most potent cholinesterase inhibitors, eight compounds also inhibited BACE1 activity at 10–18%. Based on our overall results, compounds 8 with 3-fluorobenzyl, 11 with 3-chlorobenzyl and 17 with 3-metoxy benzyl substituents on the terminal amino group stood out as the most promising for the treatment of AD; they strongly inhibited AChE and BChE, were non-toxic on HepG2, HEK293 and SH-SY5Y cells, had the potential to cross the BBB and possessed the ability to chelate biometals and/or inhibit the activity of BACE1 within a range close to the therapeutically desired degree of inhibition.
PB  - Elsevier
T2  - Chemico-Biological Interactions
T1  - Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer's disease
VL  - 382
SP  - 110620
DO  - 10.1016/j.cbi.2023.110620
ER  - 

@article{
author = "Matošević, Ana and Opsenica, Dejan and Spasić, Marta and Maraković, Nikola and Zandona, Antonio and Žunec, Suzana and Bartolić, Marija and Kovarik, Zrinka and Bosak, Anita",
year = "2023",
abstract = "The most successful therapeutic strategy in the treatment of Alzheimer's disease (AD) is directed toward increasing levels of the neurotransmitter acetylcholine (ACh) by inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the enzymes responsible for its hydrolysis. In this paper, we extended our study on 4-aminoquinolines as human cholinesterase inhibitors on twenty-six new 4-aminoquinolines containing an n-octylamino spacer on C(4) and different substituents on the terminal amino group. We evaluated the potency of new derivatives to act as multi-targeted ligands by determining their inhibition potency towards human AChE and BChE, ability to chelate biometals Fe, Cu and Zn, ability to inhibit the action of β-secretase 1 (BACE1) and their antioxidant capacity. All of the tested derivatives were very potent inhibitors of human AChE and BChE with inhibition constants (Ki) ranging from 0.0023 to 1.6 μM. Most of the compounds were estimated to be able to cross the blood-brain barrier (BBB) by passive transport and were nontoxic to human neuronal, kidney and liver cells in concentrations in which they inhibit cholinesterases. Generally, newly synthesised compounds were weak reductants compared to standard antioxidants, but all possessed a certain amount of antioxidant activity compared to tacrine. Of the eleven most potent cholinesterase inhibitors, eight compounds also inhibited BACE1 activity at 10–18%. Based on our overall results, compounds 8 with 3-fluorobenzyl, 11 with 3-chlorobenzyl and 17 with 3-metoxy benzyl substituents on the terminal amino group stood out as the most promising for the treatment of AD; they strongly inhibited AChE and BChE, were non-toxic on HepG2, HEK293 and SH-SY5Y cells, had the potential to cross the BBB and possessed the ability to chelate biometals and/or inhibit the activity of BACE1 within a range close to the therapeutically desired degree of inhibition.",
publisher = "Elsevier",
journal = "Chemico-Biological Interactions",
title = "Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer's disease",
volume = "382",
pages = "110620",
doi = "10.1016/j.cbi.2023.110620"
}

Matošević, A., Opsenica, D., Spasić, M., Maraković, N., Zandona, A., Žunec, S., Bartolić, M., Kovarik, Z.,& Bosak, A.. (2023). Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer's disease. in Chemico-Biological Interactions
Elsevier., 382, 110620.
https://doi.org/10.1016/j.cbi.2023.110620

Matošević A, Opsenica D, Spasić M, Maraković N, Zandona A, Žunec S, Bartolić M, Kovarik Z, Bosak A. Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer's disease. in Chemico-Biological Interactions. 2023;382:110620.
doi:10.1016/j.cbi.2023.110620 .

Matošević, Ana, Opsenica, Dejan, Spasić, Marta, Maraković, Nikola, Zandona, Antonio, Žunec, Suzana, Bartolić, Marija, Kovarik, Zrinka, Bosak, Anita, "Evaluation of 4-aminoquinoline derivatives with an n-octylamino spacer as potential multi-targeting ligands for the treatment of Alzheimer's disease" in Chemico-Biological Interactions, 382 (2023):110620,
https://doi.org/10.1016/j.cbi.2023.110620 . .

TY  - JOUR
AU  - Kaličanin, Nevena
AU  - Kovačević, Gordana
AU  - Spasojević, Milica
AU  - Prodanović, Olivera
AU  - Jovanović-Šanta, Suzana
AU  - Škorić, Dušan
AU  - Opsenica, Dejan
AU  - Prodanović, Radivoje
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5370
AB  - The aim of this research was to improve the operational stability and enable the reusability of ω-transaminase for synthesis of new enantiopure chiral amines of steroids. Dihydrotestosterone was used to optimize the synthetic procedure of corresponding amino-steroid on a larger scale. The obtained product 3α-amino-5α-androstan-17β-ol was isolated and characterized. The enzyme was immobilized on a methacrylate-based carrier, giving the specific activity of 1.84 U/g of dry polymer. Higher residual activity of the immobilized enzyme in comparison to the soluble form (100 % versus 35%) after 24 h incubation in 35 % dimethylformamide (DMF) was obtained. The soluble enzyme retained 19 % of the initial activity after 2 h incubation in 35 % DMF at 70 °C, while the activity of the immobilized enzyme decreased only to 75 %. Immobilized retained 85 % of initial activity after ten consecutive cycles of 3α-amino-5α-androstan-17β-ol synthesis. We have tested the specificity of the ArRMut11 variant, further increased its stability by immobilization, and used it in several cycles for the synthesis of 3α-amino-5α-androstan-17β-ol. We showed that the enzyme previously evolved for higher stability as the immobilized variant showed more increased stability and high reusability that can more effectively be applied for the biosynthesis of amino steroids.
PB  - Elsevier
T2  - Process Biochemistry
T1  - Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol
VL  - 121
SP  - 674
EP  - 680
DO  - 10.1016/j.procbio.2022.08.016
ER  - 

@article{
author = "Kaličanin, Nevena and Kovačević, Gordana and Spasojević, Milica and Prodanović, Olivera and Jovanović-Šanta, Suzana and Škorić, Dušan and Opsenica, Dejan and Prodanović, Radivoje",
year = "2022",
abstract = "The aim of this research was to improve the operational stability and enable the reusability of ω-transaminase for synthesis of new enantiopure chiral amines of steroids. Dihydrotestosterone was used to optimize the synthetic procedure of corresponding amino-steroid on a larger scale. The obtained product 3α-amino-5α-androstan-17β-ol was isolated and characterized. The enzyme was immobilized on a methacrylate-based carrier, giving the specific activity of 1.84 U/g of dry polymer. Higher residual activity of the immobilized enzyme in comparison to the soluble form (100 % versus 35%) after 24 h incubation in 35 % dimethylformamide (DMF) was obtained. The soluble enzyme retained 19 % of the initial activity after 2 h incubation in 35 % DMF at 70 °C, while the activity of the immobilized enzyme decreased only to 75 %. Immobilized retained 85 % of initial activity after ten consecutive cycles of 3α-amino-5α-androstan-17β-ol synthesis. We have tested the specificity of the ArRMut11 variant, further increased its stability by immobilization, and used it in several cycles for the synthesis of 3α-amino-5α-androstan-17β-ol. We showed that the enzyme previously evolved for higher stability as the immobilized variant showed more increased stability and high reusability that can more effectively be applied for the biosynthesis of amino steroids.",
publisher = "Elsevier",
journal = "Process Biochemistry",
title = "Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol",
volume = "121",
pages = "674-680",
doi = "10.1016/j.procbio.2022.08.016"
}

Kaličanin, N., Kovačević, G., Spasojević, M., Prodanović, O., Jovanović-Šanta, S., Škorić, D., Opsenica, D.,& Prodanović, R.. (2022). Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol. in Process Biochemistry
Elsevier., 121, 674-680.
https://doi.org/10.1016/j.procbio.2022.08.016

Kaličanin N, Kovačević G, Spasojević M, Prodanović O, Jovanović-Šanta S, Škorić D, Opsenica D, Prodanović R. Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol. in Process Biochemistry. 2022;121:674-680.
doi:10.1016/j.procbio.2022.08.016 .

Kaličanin, Nevena, Kovačević, Gordana, Spasojević, Milica, Prodanović, Olivera, Jovanović-Šanta, Suzana, Škorić, Dušan, Opsenica, Dejan, Prodanović, Radivoje, "Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol" in Process Biochemistry, 121 (2022):674-680,
https://doi.org/10.1016/j.procbio.2022.08.016 . .

TY  - JOUR
AU  - Kaličanin, Nevena
AU  - Kovačević, Gordana
AU  - Spasojević, Milica
AU  - Prodanović, Olivera
AU  - Jovanović-Šanta, Suzana
AU  - Škorić, Dušan
AU  - Opsenica, Dejan
AU  - Prodanović, Radivoje
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5545
AB  - The aim of this research was to improve the operational stability and enable the reusability of ω-transaminase for synthesis of new enantiopure chiral amines of steroids. Dihydrotestosterone was used to optimize the synthetic procedure of corresponding amino-steroid on a larger scale. The obtained product 3α-amino-5α-androstan-17β-ol was isolated and characterized. The enzyme was immobilized on a methacrylate-based carrier, giving the specific activity of 1.84 U/g of dry polymer. Higher residual activity of the immobilized enzyme in comparison to the soluble form (100 % versus 35%) after 24 h incubation in 35 % dimethylformamide (DMF) was obtained. The soluble enzyme retained 19 % of the initial activity after 2 h incubation in 35 % DMF at 70 °C, while the activity of the immobilized enzyme decreased only to 75 %. Immobilized retained 85 % of initial activity after ten consecutive cycles of 3α-amino-5α-androstan-17β-ol synthesis. We have tested the specificity of the ArRMut11 variant, further increased its stability by immobilization, and used it in several cycles for the synthesis of 3α-amino-5α-androstan-17β-ol. We showed that the enzyme previously evolved for higher stability as the immobilized variant showed more increased stability and high reusability that can more effectively be applied for the biosynthesis of amino steroids.
PB  - Elsevier
T2  - Process Biochemistry
T1  - Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol
VL  - 121
SP  - 674
EP  - 680
DO  - 10.1016/j.procbio.2022.08.016
ER  - 

@article{
author = "Kaličanin, Nevena and Kovačević, Gordana and Spasojević, Milica and Prodanović, Olivera and Jovanović-Šanta, Suzana and Škorić, Dušan and Opsenica, Dejan and Prodanović, Radivoje",
year = "2022",
abstract = "The aim of this research was to improve the operational stability and enable the reusability of ω-transaminase for synthesis of new enantiopure chiral amines of steroids. Dihydrotestosterone was used to optimize the synthetic procedure of corresponding amino-steroid on a larger scale. The obtained product 3α-amino-5α-androstan-17β-ol was isolated and characterized. The enzyme was immobilized on a methacrylate-based carrier, giving the specific activity of 1.84 U/g of dry polymer. Higher residual activity of the immobilized enzyme in comparison to the soluble form (100 % versus 35%) after 24 h incubation in 35 % dimethylformamide (DMF) was obtained. The soluble enzyme retained 19 % of the initial activity after 2 h incubation in 35 % DMF at 70 °C, while the activity of the immobilized enzyme decreased only to 75 %. Immobilized retained 85 % of initial activity after ten consecutive cycles of 3α-amino-5α-androstan-17β-ol synthesis. We have tested the specificity of the ArRMut11 variant, further increased its stability by immobilization, and used it in several cycles for the synthesis of 3α-amino-5α-androstan-17β-ol. We showed that the enzyme previously evolved for higher stability as the immobilized variant showed more increased stability and high reusability that can more effectively be applied for the biosynthesis of amino steroids.",
publisher = "Elsevier",
journal = "Process Biochemistry",
title = "Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol",
volume = "121",
pages = "674-680",
doi = "10.1016/j.procbio.2022.08.016"
}

Kaličanin, N., Kovačević, G., Spasojević, M., Prodanović, O., Jovanović-Šanta, S., Škorić, D., Opsenica, D.,& Prodanović, R.. (2022). Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol. in Process Biochemistry
Elsevier., 121, 674-680.
https://doi.org/10.1016/j.procbio.2022.08.016

Kaličanin N, Kovačević G, Spasojević M, Prodanović O, Jovanović-Šanta S, Škorić D, Opsenica D, Prodanović R. Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol. in Process Biochemistry. 2022;121:674-680.
doi:10.1016/j.procbio.2022.08.016 .

Kaličanin, Nevena, Kovačević, Gordana, Spasojević, Milica, Prodanović, Olivera, Jovanović-Šanta, Suzana, Škorić, Dušan, Opsenica, Dejan, Prodanović, Radivoje, "Immobilization of ArRMut11 omega-transaminase for increased operational stability and reusability in the synthesis of 3α-amino-5α-androstan-17β-ol" in Process Biochemistry, 121 (2022):674-680,
https://doi.org/10.1016/j.procbio.2022.08.016 . .

TY  - JOUR
AU  - Komatović, Katarina
AU  - Matošević, Ana
AU  - Terzić-Jovanović, Nataša
AU  - Žunec, Suzana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Maraković, Nikola
AU  - Bosak, Anita
AU  - Opsenica, Dejan
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5232
AB  - Considering that acetylcholinesterase (AChE) inhibition is the most important mode of action expected of a potential drug used for the treatment of symptoms of Alzheimer’s disease (AD), our previous pilot study of 4-aminoquinolines as potential human cholinesterase inhibitors was extended to twenty-two new structurally distinct 4-aminoquinolines bearing an adamantane moiety. Inhibition studies revealed that all of the compounds were very potent inhibitors of AChE and butyrylcholinesterase (BChE), with inhibition constants (Ki) ranging between 0.075 and 25 µM. The tested compounds exhibited a modest selectivity between the two cholinesterases; the most selective for BChE was compound 14, which displayed a 10 times higher preference, while compound 19 was a 5.8 times more potent inhibitor of AChE. Most of the compounds were estimated to be able to cross the blood–brain barrier (BBB) by passive transport. Evaluation of druglikeness singled out fourteen compounds with possible oral route of administration. The tested compounds displayed modest but generally higher antioxidant activity than the structurally similar AD drug tacrine. Compound 19 showed the highest reducing power, comparable to those of standard antioxidants. Considering their simple structure, high inhibition of AChE and BChE, and ability to cross the BBB, 4-aminoquinoline-based adamantanes show promise as structural scaffolds for further design of novel central nervous system drugs. Among them, two compounds stand out: compound 5 as the most potent inhibitor of both cholinesterases with a Ki constant in low nano molar range and the potential to cross the BBB, and compound 8, which met all our requirements, including high cholinesterase inhibition, good oral bioavailability, and antioxidative effect. The QSAR model revealed that AChE and BChE inhibition was mainly influenced by the ring and topological descriptors MCD, Nnum, RP, and RSIpw3, which defined the shape, conformational flexibility, and surface properties of the molecules
PB  - MDPI
T2  - Pharmaceutics
T1  - 4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer’s Disease
VL  - 14
IS  - 6
SP  - 1305
DO  - 10.3390/pharmaceutics14061305
ER  - 

@article{
author = "Komatović, Katarina and Matošević, Ana and Terzić-Jovanović, Nataša and Žunec, Suzana and Šegan, Sandra and Zlatović, Mario and Maraković, Nikola and Bosak, Anita and Opsenica, Dejan",
year = "2022",
abstract = "Considering that acetylcholinesterase (AChE) inhibition is the most important mode of action expected of a potential drug used for the treatment of symptoms of Alzheimer’s disease (AD), our previous pilot study of 4-aminoquinolines as potential human cholinesterase inhibitors was extended to twenty-two new structurally distinct 4-aminoquinolines bearing an adamantane moiety. Inhibition studies revealed that all of the compounds were very potent inhibitors of AChE and butyrylcholinesterase (BChE), with inhibition constants (Ki) ranging between 0.075 and 25 µM. The tested compounds exhibited a modest selectivity between the two cholinesterases; the most selective for BChE was compound 14, which displayed a 10 times higher preference, while compound 19 was a 5.8 times more potent inhibitor of AChE. Most of the compounds were estimated to be able to cross the blood–brain barrier (BBB) by passive transport. Evaluation of druglikeness singled out fourteen compounds with possible oral route of administration. The tested compounds displayed modest but generally higher antioxidant activity than the structurally similar AD drug tacrine. Compound 19 showed the highest reducing power, comparable to those of standard antioxidants. Considering their simple structure, high inhibition of AChE and BChE, and ability to cross the BBB, 4-aminoquinoline-based adamantanes show promise as structural scaffolds for further design of novel central nervous system drugs. Among them, two compounds stand out: compound 5 as the most potent inhibitor of both cholinesterases with a Ki constant in low nano molar range and the potential to cross the BBB, and compound 8, which met all our requirements, including high cholinesterase inhibition, good oral bioavailability, and antioxidative effect. The QSAR model revealed that AChE and BChE inhibition was mainly influenced by the ring and topological descriptors MCD, Nnum, RP, and RSIpw3, which defined the shape, conformational flexibility, and surface properties of the molecules",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer’s Disease",
volume = "14",
number = "6",
pages = "1305",
doi = "10.3390/pharmaceutics14061305"
}

Komatović, K., Matošević, A., Terzić-Jovanović, N., Žunec, S., Šegan, S., Zlatović, M., Maraković, N., Bosak, A.,& Opsenica, D.. (2022). 4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer’s Disease. in Pharmaceutics
MDPI., 14(6), 1305.
https://doi.org/10.3390/pharmaceutics14061305

Komatović K, Matošević A, Terzić-Jovanović N, Žunec S, Šegan S, Zlatović M, Maraković N, Bosak A, Opsenica D. 4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer’s Disease. in Pharmaceutics. 2022;14(6):1305.
doi:10.3390/pharmaceutics14061305 .

Komatović, Katarina, Matošević, Ana, Terzić-Jovanović, Nataša, Žunec, Suzana, Šegan, Sandra, Zlatović, Mario, Maraković, Nikola, Bosak, Anita, Opsenica, Dejan, "4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer’s Disease" in Pharmaceutics, 14, no. 6 (2022):1305,
https://doi.org/10.3390/pharmaceutics14061305 . .

TY  - CHAP
AU  - Senerovic, Lidija
AU  - Moric, Ivana
AU  - Milivojevic, Dusan
AU  - Opsenica, Dejan
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4459
AB  - The rapid emergence of antibiotic-resistant pathogens presents a global healthcare challenge. Bacteria control their virulence, motility, and biofilm formation, all of them being required for establishing pathogenicity, through a cell density-dependent communication system known as quorum sensing (QS). QS comprises production of extracellular signaling molecules, their detection, and population-wide response involving regulation of the virulence genes expression. Inhibition of QS affects virulence and reduces harmful effects to the host and as such presents a promising strategy to fight antibiotic-resistant infections. Multiresistant Pseudomonas aeruginosa belogns to the group of most critical pathogens for which the introduction of new therapeutics is imperative. In the search for novel therapeutics nature continues to be inexhaustible source of bioactive scaffolds, which provide the bases for structure-based rational drug design enabling further exploitation of diverse natural structures. This review describes bacterial QS systems, highlights strategies for their manipulation, overviews nature-inspired antivirulence molecules primarily against P. aeruginosa, and discusses their perspectives.
PB  - Elsevier
T2  - Biodiversity and Biomedicine
T1  - Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections
SP  - 497
EP  - 523
DO  - 10.1016/B978-0-12-819541-3.00025-6
ER  - 

@inbook{
author = "Senerovic, Lidija and Moric, Ivana and Milivojevic, Dusan and Opsenica, Dejan",
year = "2020",
abstract = "The rapid emergence of antibiotic-resistant pathogens presents a global healthcare challenge. Bacteria control their virulence, motility, and biofilm formation, all of them being required for establishing pathogenicity, through a cell density-dependent communication system known as quorum sensing (QS). QS comprises production of extracellular signaling molecules, their detection, and population-wide response involving regulation of the virulence genes expression. Inhibition of QS affects virulence and reduces harmful effects to the host and as such presents a promising strategy to fight antibiotic-resistant infections. Multiresistant Pseudomonas aeruginosa belogns to the group of most critical pathogens for which the introduction of new therapeutics is imperative. In the search for novel therapeutics nature continues to be inexhaustible source of bioactive scaffolds, which provide the bases for structure-based rational drug design enabling further exploitation of diverse natural structures. This review describes bacterial QS systems, highlights strategies for their manipulation, overviews nature-inspired antivirulence molecules primarily against P. aeruginosa, and discusses their perspectives.",
publisher = "Elsevier",
journal = "Biodiversity and Biomedicine",
booktitle = "Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections",
pages = "497-523",
doi = "10.1016/B978-0-12-819541-3.00025-6"
}

Senerovic, L., Moric, I., Milivojevic, D.,& Opsenica, D.. (2020). Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections. in Biodiversity and Biomedicine
Elsevier., 497-523.
https://doi.org/10.1016/B978-0-12-819541-3.00025-6

Senerovic L, Moric I, Milivojevic D, Opsenica D. Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections. in Biodiversity and Biomedicine. 2020;:497-523.
doi:10.1016/B978-0-12-819541-3.00025-6 .

Senerovic, Lidija, Moric, Ivana, Milivojevic, Dusan, Opsenica, Dejan, "Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections" in Biodiversity and Biomedicine (2020):497-523,
https://doi.org/10.1016/B978-0-12-819541-3.00025-6 . .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - JOUR
AU  - Aleksic, Ivana
AU  - Jeremić, Jelena
AU  - Milivojevic, Dusan
AU  - Ilić-Tomić, Tatjana
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3198
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3341
AB  - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
PB  - American Chemical Society (ACS)
T2  - ACS Chemical Biology
T1  - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
VL  - 14
IS  - 12
SP  - 2800
EP  - 2809
DO  - 10.1021/acschembio.9b00682
ER  - 

@article{
author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan and Senerovic, Lidija",
year = "2019",
abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.",
publisher = "American Chemical Society (ACS)",
journal = "ACS Chemical Biology",
title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa",
volume = "14",
number = "12",
pages = "2800-2809",
doi = "10.1021/acschembio.9b00682"
}

Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology
American Chemical Society (ACS)., 14(12), 2800-2809.
https://doi.org/10.1021/acschembio.9b00682

Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;14(12):2800-2809.
doi:10.1021/acschembio.9b00682 .

Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology, 14, no. 12 (2019):2800-2809,
https://doi.org/10.1021/acschembio.9b00682 . .

TY  - JOUR
AU  - Janakiev, Tamara
AU  - Dimkić, Ivica
AU  - Unković, Nikola
AU  - Ljaljević Grbić, Milica
AU  - Opsenica, Dejan
AU  - Gašić, Uroš
AU  - Stanković, Slaviša
AU  - Berić, Tanja
PY  - 2019
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2019.02287/abstract
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3093
AB  - European plum (Prunus domestica L.) is a significant commercial crop in Serbia in terms of total fruit production, and it is traditionally processed into slivovitz brandy. The annual plum yields in Serbia is strongly affected by Monilinia laxa, causing brown rot in stone fruits. The fungal communities associated with leaves and fruits of four local Serbian plum cultivars (Požegača, Ranka, Lepotica and Rodna) were investigated in two phenological stages during early (May) and late (July) fruit maturation. Alpha diversity indices showed that fungal communities were heterogeneous and Beta diversity indicated that autochthonous fungal communities depended upon seasonal changes and the cultivars themselves. The phylum Ascomycota was the most abundant in all samples, with relative abundance (RA) between 46% in the Požegača cultivar (May) and 89% in the Lepotica cultivar (July). The most abundant genus for all plum cultivars in May was Aureobasidium, with RA from 19.27 to 33.69%, followed by Cryptococcus, with 4.8 to 48.80%. In July, besides Cryptococcus, different genera (Metschnikowia, Fusarium and Hanseniaspora) were dominant on particular cultivars. Among all cultivable fungi, molecular identification of 11 M. laxa isolates from four plum cultivars was performed simultaneously. Bacterial isolates from the plum phyllosphere were tested for their potential antifungal activity against indigenous M. laxa isolates. The most potent antagonist, P4/16_1 was identified as Pseudomonas synxantha, which reduced mycelial growth of M. laxa from 80 to 87.5%. The production of volatile organic compounds was observed as well. Screening for the antibiotic coding gene was positive for phenazine-1-carboxylic acid, and benzene extraction of P. synxantha-active compounds was done. The crude benzene extract exhibited 57–63% inhibition of mycelial growth. The conducted LC/MS analysis of the crude extract confirmed the presence of phenazine derivatives amongst other compounds. Scanning electron microscopy revealed morpho-physiological changes in the hyphae of M. laxa isolates caused by the cell culture and the P. synxantha P4/16_1 crude benzene extract. This is first report of antagonistic activity of P. synxantha against M. laxa induced by diffusible and volatile antifungal compounds, and it appears to be a promising candidate for use as a biocontrol agent against brown rot-causing fungi.
PB  - Frontiers
T2  - Frontiers in Microbiology
T1  - Phyllosphere fungal communities of plum and antifungal activity of indigenous phenazine-producing Pseudomonas synxantha against Monilinia laxa
VL  - 10
SP  - 2287
DO  - 10.3389/fmicb.2019.02287
ER  - 

@article{
author = "Janakiev, Tamara and Dimkić, Ivica and Unković, Nikola and Ljaljević Grbić, Milica and Opsenica, Dejan and Gašić, Uroš and Stanković, Slaviša and Berić, Tanja",
year = "2019",
abstract = "European plum (Prunus domestica L.) is a significant commercial crop in Serbia in terms of total fruit production, and it is traditionally processed into slivovitz brandy. The annual plum yields in Serbia is strongly affected by Monilinia laxa, causing brown rot in stone fruits. The fungal communities associated with leaves and fruits of four local Serbian plum cultivars (Požegača, Ranka, Lepotica and Rodna) were investigated in two phenological stages during early (May) and late (July) fruit maturation. Alpha diversity indices showed that fungal communities were heterogeneous and Beta diversity indicated that autochthonous fungal communities depended upon seasonal changes and the cultivars themselves. The phylum Ascomycota was the most abundant in all samples, with relative abundance (RA) between 46% in the Požegača cultivar (May) and 89% in the Lepotica cultivar (July). The most abundant genus for all plum cultivars in May was Aureobasidium, with RA from 19.27 to 33.69%, followed by Cryptococcus, with 4.8 to 48.80%. In July, besides Cryptococcus, different genera (Metschnikowia, Fusarium and Hanseniaspora) were dominant on particular cultivars. Among all cultivable fungi, molecular identification of 11 M. laxa isolates from four plum cultivars was performed simultaneously. Bacterial isolates from the plum phyllosphere were tested for their potential antifungal activity against indigenous M. laxa isolates. The most potent antagonist, P4/16_1 was identified as Pseudomonas synxantha, which reduced mycelial growth of M. laxa from 80 to 87.5%. The production of volatile organic compounds was observed as well. Screening for the antibiotic coding gene was positive for phenazine-1-carboxylic acid, and benzene extraction of P. synxantha-active compounds was done. The crude benzene extract exhibited 57–63% inhibition of mycelial growth. The conducted LC/MS analysis of the crude extract confirmed the presence of phenazine derivatives amongst other compounds. Scanning electron microscopy revealed morpho-physiological changes in the hyphae of M. laxa isolates caused by the cell culture and the P. synxantha P4/16_1 crude benzene extract. This is first report of antagonistic activity of P. synxantha against M. laxa induced by diffusible and volatile antifungal compounds, and it appears to be a promising candidate for use as a biocontrol agent against brown rot-causing fungi.",
publisher = "Frontiers",
journal = "Frontiers in Microbiology",
title = "Phyllosphere fungal communities of plum and antifungal activity of indigenous phenazine-producing Pseudomonas synxantha against Monilinia laxa",
volume = "10",
pages = "2287",
doi = "10.3389/fmicb.2019.02287"
}

Janakiev, T., Dimkić, I., Unković, N., Ljaljević Grbić, M., Opsenica, D., Gašić, U., Stanković, S.,& Berić, T.. (2019). Phyllosphere fungal communities of plum and antifungal activity of indigenous phenazine-producing Pseudomonas synxantha against Monilinia laxa. in Frontiers in Microbiology
Frontiers., 10, 2287.
https://doi.org/10.3389/fmicb.2019.02287

Janakiev T, Dimkić I, Unković N, Ljaljević Grbić M, Opsenica D, Gašić U, Stanković S, Berić T. Phyllosphere fungal communities of plum and antifungal activity of indigenous phenazine-producing Pseudomonas synxantha against Monilinia laxa. in Frontiers in Microbiology. 2019;10:2287.
doi:10.3389/fmicb.2019.02287 .

Janakiev, Tamara, Dimkić, Ivica, Unković, Nikola, Ljaljević Grbić, Milica, Opsenica, Dejan, Gašić, Uroš, Stanković, Slaviša, Berić, Tanja, "Phyllosphere fungal communities of plum and antifungal activity of indigenous phenazine-producing Pseudomonas synxantha against Monilinia laxa" in Frontiers in Microbiology, 10 (2019):2287,
https://doi.org/10.3389/fmicb.2019.02287 . .

TY  - JOUR
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2886
AB  - Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase
VL  - 308
SP  - 101
EP  - 109
DO  - 10.1016/j.cbi.2019.05.024
ER  - 

@article{
author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka",
year = "2019",
abstract = "Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase",
volume = "308",
pages = "101-109",
doi = "10.1016/j.cbi.2019.05.024"
}

Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 308, 101-109.
https://doi.org/10.1016/j.cbi.2019.05.024

Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions. 2019;308:101-109.
doi:10.1016/j.cbi.2019.05.024 .

Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase" in Chemico-Biological Interactions, 308 (2019):101-109,
https://doi.org/10.1016/j.cbi.2019.05.024 . .

TY  - JOUR
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2905
AB  - Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase
VL  - 308
SP  - 101
EP  - 109
DO  - 10.1016/j.cbi.2019.05.024
ER  - 

@article{
author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka",
year = "2019",
abstract = "Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7)were synthesised and tested as inhibitors of human acetylcholinesterase (AChE)and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K i )ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chain length resulted in a decrease in AChE inhibition by 5–20 times. Docking studies revealed that the quinoline group within the AChE active site was positioned in the choline binding site, while the C(4)-amino group substituents, depending on their lipophilicity, could establish hydrogen bonds or π-interactions with residues of the peripheral anionic site. The most potent inhibitors of BChE were compounds with the most voluminous substituent on C(4)-amino group (adamantyl)or those with a stronger electron withdrawing substituent on C(7)(trifluormethyl group). Based on AChE inhibition, compounds with an n-octylamino chain or adamantyl substituent were shown to possess the capacity for further development as potential drugs for treatment of neurodegenerative diseases. © 2019 Elsevier B.V.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase",
volume = "308",
pages = "101-109",
doi = "10.1016/j.cbi.2019.05.024"
}

Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2019). Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 308, 101-109.
https://doi.org/10.1016/j.cbi.2019.05.024

Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase. in Chemico-Biological Interactions. 2019;308:101-109.
doi:10.1016/j.cbi.2019.05.024 .

Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase" in Chemico-Biological Interactions, 308 (2019):101-109,
https://doi.org/10.1016/j.cbi.2019.05.024 . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3205
AB  - Among widely used chromatographic methods modern thin-layer chromatography is not only the
simplest to perform but is also considered as respectable analytical method in various phases of
drug discovery and development processes such as monitoring of synthesis, identification of bioactive
substances from various natural sources and their isolation and purification, determination
of lipophilicity and other physico-chemical parameters, quantitative structure-activity relationship
studies, bioautography, as well as qualitative and quantitative analysis of drugs and their metabolites. An overview of recently published papers dealing with application of thin-layer chromatography in medicinal chemistry is presented.
PB  - Taylor & Francis Inc.
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Thin-layer chromatography in medicinal chemistry
VL  - 42
IS  - 9-10
SP  - 238
EP  - 248
DO  - 10.1080/10826076.2019.1585615
ER  - 

@article{
author = "Šegan, Sandra and Opsenica, Dejan and Milojković-Opsenica, Dušanka",
year = "2019",
abstract = "Among widely used chromatographic methods modern thin-layer chromatography is not only the
simplest to perform but is also considered as respectable analytical method in various phases of
drug discovery and development processes such as monitoring of synthesis, identification of bioactive
substances from various natural sources and their isolation and purification, determination
of lipophilicity and other physico-chemical parameters, quantitative structure-activity relationship
studies, bioautography, as well as qualitative and quantitative analysis of drugs and their metabolites. An overview of recently published papers dealing with application of thin-layer chromatography in medicinal chemistry is presented.",
publisher = "Taylor & Francis Inc.",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Thin-layer chromatography in medicinal chemistry",
volume = "42",
number = "9-10",
pages = "238-248",
doi = "10.1080/10826076.2019.1585615"
}

Šegan, S., Opsenica, D.,& Milojković-Opsenica, D.. (2019). Thin-layer chromatography in medicinal chemistry. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc.., 42(9-10), 238-248.
https://doi.org/10.1080/10826076.2019.1585615

Šegan S, Opsenica D, Milojković-Opsenica D. Thin-layer chromatography in medicinal chemistry. in Journal of Liquid Chromatography & Related Technologies. 2019;42(9-10):238-248.
doi:10.1080/10826076.2019.1585615 .

Šegan, Sandra, Opsenica, Dejan, Milojković-Opsenica, Dušanka, "Thin-layer chromatography in medicinal chemistry" in Journal of Liquid Chromatography & Related Technologies, 42, no. 9-10 (2019):238-248,
https://doi.org/10.1080/10826076.2019.1585615 . .

TY  - CHAP
AU  - Senerovic, Lidija
AU  - Opsenica, Dejan
AU  - Moric, Ivana
AU  - Aleksic, Ivana
AU  - Spasić, Marta
AU  - Vasiljevic, Branka
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3094
AB  - Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.
PB  - Springer Nature
T2  - Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
T1  - Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents
DO  - 10.1007/5584_2019_428
ER  - 

@inbook{
author = "Senerovic, Lidija and Opsenica, Dejan and Moric, Ivana and Aleksic, Ivana and Spasić, Marta and Vasiljevic, Branka",
year = "2019",
abstract = "Infective diseases have become health threat of
a global proportion due to appearance and
spread of microorganisms resistant to majority
of therapeutics currently used for their treatment.
Therefore, there is a constant need for
development of new antimicrobial agents, as
well as novel therapeutic strategies.
Quinolines and quinolones, isolated from
plants, animals, and microorganisms, have
demonstrated numerous biological activities
such as antimicrobial, insecticidal, antiinflammatory,
antiplatelet, and antitumor. For
more than two centuries quinoline/quinolone
moiety has been used as a scaffold for drug
development and even today it represents an
inexhaustible inspiration for design and development
of novel semi-synthetic or synthetic
agents exhibiting broad spectrum of
bioactivities. The structural diversity of
synthetized compounds provides high and
selective activity attained through different
mechanisms of action, as well as low toxicity
on human cells. This review describes quinoline
and quinolone derivatives with
antibacterial, antifungal, anti-virulent,
antiviral, and anti-parasitic activities with the
focus on the last 10 years literature.",
publisher = "Springer Nature",
journal = "Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health",
booktitle = "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents",
doi = "10.1007/5584_2019_428"
}

Senerovic, L., Opsenica, D., Moric, I., Aleksic, I., Spasić, M.,& Vasiljevic, B.. (2019). Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health
Springer Nature..
https://doi.org/10.1007/5584_2019_428

Senerovic L, Opsenica D, Moric I, Aleksic I, Spasić M, Vasiljevic B. Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents. in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health. 2019;.
doi:10.1007/5584_2019_428 .

Senerovic, Lidija, Opsenica, Dejan, Moric, Ivana, Aleksic, Ivana, Spasić, Marta, Vasiljevic, Branka, "Quinolines and Quinolones as Antibacterial, Antifungal, Antivirulence, Antiviral and Anti-parasitic Agents" in Advances in Experimental Medicine and Biology - Advances in Microbiology, Infectious Diseases and Public Health (2019),
https://doi.org/10.1007/5584_2019_428 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Ristivojević, Petar
AU  - Pavić, Aleksandar
AU  - Radojević, Ivana
AU  - Čomić, Ljiljana R.
AU  - Vasiljević, Branka
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
AU  - Šenerović, Lidija
PY  - 2018
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/2932
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3139
AB  - Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts
VL  - 222
SP  - 148
EP  - 158
DO  - 10.1016/j.jep.2018.05.005
ER  - 

@article{
author = "Aleksić, Ivana and Ristivojević, Petar and Pavić, Aleksandar and Radojević, Ivana and Čomić, Ljiljana R. and Vasiljević, Branka and Opsenica, Dejan and Milojković-Opsenica, Dušanka and Šenerović, Lidija",
year = "2018",
abstract = "Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts",
volume = "222",
pages = "148-158",
doi = "10.1016/j.jep.2018.05.005"
}

Aleksić, I., Ristivojević, P., Pavić, A., Radojević, I., Čomić, L. R., Vasiljević, B., Opsenica, D., Milojković-Opsenica, D.,& Šenerović, L.. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 222, 148-158.
https://doi.org/10.1016/j.jep.2018.05.005

Aleksić I, Ristivojević P, Pavić A, Radojević I, Čomić LR, Vasiljević B, Opsenica D, Milojković-Opsenica D, Šenerović L. Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology. 2018;222:148-158.
doi:10.1016/j.jep.2018.05.005 .

Aleksić, Ivana, Ristivojević, Petar, Pavić, Aleksandar, Radojević, Ivana, Čomić, Ljiljana R., Vasiljević, Branka, Opsenica, Dejan, Milojković-Opsenica, Dušanka, Šenerović, Lidija, "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts" in Journal of Ethnopharmacology, 222 (2018):148-158,
https://doi.org/10.1016/j.jep.2018.05.005 . .

TY  - CONF
AU  - Dragičević, Vesna
AU  - Opsenica, Dejan
AU  - Mesarović, Jelena
AU  - Brankov, Milan
AU  - Simić, Milena
AU  - Kravić, Natalija
AU  - Milojković-Opsenica, Dušanka
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7097
AB  - Germination is one of the most sensitive phases in growth of agricultural plants, where optimal conditions in temperature and water accessibility are required. Seedlings are particularly sensitive to environmental stressors, especially when maize lines are considered. They tend to germinate and grow slower, have poorer adaptability to stress and seeds could lose germination ability relative fast. Application of natural or synthetic substances could increases maize vigor, particularly of seeds with poor viability. It is proven that some stimulators positively affect growth, water absorption and antioxidative response of plants [1-4]. The aim of experiment was to examine the influence of four mixed tetraoxanes on germination and early growth (seven-day old seedlings) of maize inbred line with low germination ability (<50%).
PB  - Society of Physical Chemists of Serbia
C3  - Proceedings - Physical Chemistry 2018 - 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24-28, 2018, Belgrade
T1  - The effect of some mixed tetraoxanes on germination and antioxidants in maize seedlings
VL  - 1
SP  - 547
EP  - 550
UR  - https://hdl.handle.net/21.15107/rcub_cer_7097
ER  - 

@conference{
author = "Dragičević, Vesna and Opsenica, Dejan and Mesarović, Jelena and Brankov, Milan and Simić, Milena and Kravić, Natalija and Milojković-Opsenica, Dušanka",
year = "2018",
abstract = "Germination is one of the most sensitive phases in growth of agricultural plants, where optimal conditions in temperature and water accessibility are required. Seedlings are particularly sensitive to environmental stressors, especially when maize lines are considered. They tend to germinate and grow slower, have poorer adaptability to stress and seeds could lose germination ability relative fast. Application of natural or synthetic substances could increases maize vigor, particularly of seeds with poor viability. It is proven that some stimulators positively affect growth, water absorption and antioxidative response of plants [1-4]. The aim of experiment was to examine the influence of four mixed tetraoxanes on germination and early growth (seven-day old seedlings) of maize inbred line with low germination ability (<50%).",
publisher = "Society of Physical Chemists of Serbia",
journal = "Proceedings - Physical Chemistry 2018 - 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24-28, 2018, Belgrade",
title = "The effect of some mixed tetraoxanes on germination and antioxidants in maize seedlings",
volume = "1",
pages = "547-550",
url = "https://hdl.handle.net/21.15107/rcub_cer_7097"
}

Dragičević, V., Opsenica, D., Mesarović, J., Brankov, M., Simić, M., Kravić, N.,& Milojković-Opsenica, D.. (2018). The effect of some mixed tetraoxanes on germination and antioxidants in maize seedlings. in Proceedings - Physical Chemistry 2018 - 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24-28, 2018, Belgrade
Society of Physical Chemists of Serbia., 1, 547-550.
https://hdl.handle.net/21.15107/rcub_cer_7097

Dragičević V, Opsenica D, Mesarović J, Brankov M, Simić M, Kravić N, Milojković-Opsenica D. The effect of some mixed tetraoxanes on germination and antioxidants in maize seedlings. in Proceedings - Physical Chemistry 2018 - 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24-28, 2018, Belgrade. 2018;1:547-550.
https://hdl.handle.net/21.15107/rcub_cer_7097 .

Dragičević, Vesna, Opsenica, Dejan, Mesarović, Jelena, Brankov, Milan, Simić, Milena, Kravić, Natalija, Milojković-Opsenica, Dušanka, "The effect of some mixed tetraoxanes on germination and antioxidants in maize seedlings" in Proceedings - Physical Chemistry 2018 - 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 24-28, 2018, Belgrade, 1 (2018):547-550,
https://hdl.handle.net/21.15107/rcub_cer_7097 .

TY  - CONF
AU  - Bosak, Anita
AU  - Opsenica, Dejan
AU  - Šinko, Goran
AU  - Zlatar, Matija
AU  - Kovarik, Zrinka
PY  - 2018
UR  - https://mmsl.cz/artkey/mms-201888-0083.php
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3216
AB  - We synthesised eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7) carbon of 4-aminoquinoline, and tested their potency to inhibit human AChE and BChE. All of the compounds reversibly inhibited both enzymes with dissociation inhibition (Ki) constants from 0.50 to 50 µM exhibiting selectivity. In other words, for all compounds, AChE exhibited higher affinity than BChE. The most potent inhibitors of AChE were compounds with an octyl chain or adamantane, regardless of the group in position C(7). The shortening of the chain length caused the AChE inhibition decrease by 5-20 times. Docking studies made it clear that the high AChE affinity resulted from simultaneous interactions of the quinoline group with aromatic residues of both the catalytic active site and the peripheral site. In conclusion, the inhibition potency and selectivity classify several novel compounds as leads for further modification and optimization towards the development of new inhibitors of AChE and potential drugs for treatment of neurodegenerative diseases.
PB  - Faculty of Military Health Sciences, Czech Republic
C3  - Military Medical Science Letters
T1  - 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity
VL  - 87
IS  - Suppl. 1
SP  - 83
EP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_cer_3216
ER  - 

@conference{
author = "Bosak, Anita and Opsenica, Dejan and Šinko, Goran and Zlatar, Matija and Kovarik, Zrinka",
year = "2018",
abstract = "We synthesised eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7) carbon of 4-aminoquinoline, and tested their potency to inhibit human AChE and BChE. All of the compounds reversibly inhibited both enzymes with dissociation inhibition (Ki) constants from 0.50 to 50 µM exhibiting selectivity. In other words, for all compounds, AChE exhibited higher affinity than BChE. The most potent inhibitors of AChE were compounds with an octyl chain or adamantane, regardless of the group in position C(7). The shortening of the chain length caused the AChE inhibition decrease by 5-20 times. Docking studies made it clear that the high AChE affinity resulted from simultaneous interactions of the quinoline group with aromatic residues of both the catalytic active site and the peripheral site. In conclusion, the inhibition potency and selectivity classify several novel compounds as leads for further modification and optimization towards the development of new inhibitors of AChE and potential drugs for treatment of neurodegenerative diseases.",
publisher = "Faculty of Military Health Sciences, Czech Republic",
journal = "Military Medical Science Letters",
title = "4-Aminoqionolines as reversible inhibitors of human cholinesterase activity",
volume = "87",
number = "Suppl. 1",
pages = "83-83",
url = "https://hdl.handle.net/21.15107/rcub_cer_3216"
}

Bosak, A., Opsenica, D., Šinko, G., Zlatar, M.,& Kovarik, Z.. (2018). 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity. in Military Medical Science Letters
Faculty of Military Health Sciences, Czech Republic., 87(Suppl. 1), 83-83.
https://hdl.handle.net/21.15107/rcub_cer_3216

Bosak A, Opsenica D, Šinko G, Zlatar M, Kovarik Z. 4-Aminoqionolines as reversible inhibitors of human cholinesterase activity. in Military Medical Science Letters. 2018;87(Suppl. 1):83-83.
https://hdl.handle.net/21.15107/rcub_cer_3216 .

Bosak, Anita, Opsenica, Dejan, Šinko, Goran, Zlatar, Matija, Kovarik, Zrinka, "4-Aminoqionolines as reversible inhibitors of human cholinesterase activity" in Military Medical Science Letters, 87, no. Suppl. 1 (2018):83-83,
https://hdl.handle.net/21.15107/rcub_cer_3216 .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Ristivojevic, Petar
AU  - Pavić, Aleksandar
AU  - Radojevic, Ivana
AU  - Čomić, Ljiljana R.
AU  - Vasiljevic, Branka
AU  - Opsenica, Dejan
AU  - Milojković-Opsenica, Dušanka
AU  - Senerovic, Lidija
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2310
AB  - Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.
PB  - Elsevier Ireland Ltd, Clare
T2  - Journal of Ethnopharmacology
T1  - Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts
VL  - 222
SP  - 148
EP  - 158
DO  - 10.1016/j.jep.2018.05.005
ER  - 

@article{
author = "Aleksić, Ivana and Ristivojevic, Petar and Pavić, Aleksandar and Radojevic, Ivana and Čomić, Ljiljana R. and Vasiljevic, Branka and Opsenica, Dejan and Milojković-Opsenica, Dušanka and Senerovic, Lidija",
year = "2018",
abstract = "Ethnopharmacological relevance: Trapa natans L. (water chestnut or water caltrop) is a widespread aquatic plant, which has been cultivated for food and traditional medicine since ancient times. Pharmacological studies showed that water chestnut exhibits the wide range of biological activities, such as antimicrobial, antioxidative, analgesic, anti-inflammatory, as well as antiulcer. Aim of the study: Evaluation of anti-virulence potential and toxicity of T. natans methanol (TnM), acetone (TnA) and ethyl acetate (TnEA) leaf extracts. Materials and methods: The anti-quorum sensing activity of Tn extracts was addressed by measuring their effects on biofilm formation, swarming motility and pyocyanin and elastase production in Pseudomonas aeruginosa. Specific P. aeruginosa biosensors were used to identify which of the signaling pathways were affected. The lethal and developmental toxicity of extracts were addressed in vivo using the zebrafish (Danio rerio) model system. The phenolic composition of T. natans leafs extracts was analyzed by a linear ion trap-OrbiTrap hybrid mass spectrometer (LTQ OrbiTrapMS) and UHPLC system configured with a diode array detector (DAD) hyphenated with the triple quadrupole mass spectrometer. Results: Subinhibitory concentrations of Tn leaf extracts (0.2 MIC) inhibited pyocyanin and elastase production up to 50% and 60%, respectively, and reduced swarming zones, comparing to non-treated P. aeruginosa. TnA inhibited biofilm formation by 15%, TnM showed a stimulatory effect on biofilm formation up to 20%, while TnEA showed no effect. The bioactive concentrations of TnM and TnA were not toxic in the zebrafish model system. Twenty-two phenolic compounds were tentatively identified in TnM, where thirteen of them were identified in T. natans for the first time. Tn extracts, as well as their major components, ellagic and ferulic acids, demonstrated the ability to interfere with P. aeruginosa Las and PQS signaling pathways. Conclusions: This study demonstrates anti-virulence potential of Tn leaf extracts against medically important pathogen P. aeruginosa and confirms the ethnopharmacological application of this plant against microbial infections.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Journal of Ethnopharmacology",
title = "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts",
volume = "222",
pages = "148-158",
doi = "10.1016/j.jep.2018.05.005"
}

Aleksić, I., Ristivojevic, P., Pavić, A., Radojevic, I., Čomić, L. R., Vasiljevic, B., Opsenica, D., Milojković-Opsenica, D.,& Senerovic, L.. (2018). Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology
Elsevier Ireland Ltd, Clare., 222, 148-158.
https://doi.org/10.1016/j.jep.2018.05.005

Aleksić I, Ristivojevic P, Pavić A, Radojevic I, Čomić LR, Vasiljevic B, Opsenica D, Milojković-Opsenica D, Senerovic L. Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts. in Journal of Ethnopharmacology. 2018;222:148-158.
doi:10.1016/j.jep.2018.05.005 .

Aleksić, Ivana, Ristivojevic, Petar, Pavić, Aleksandar, Radojevic, Ivana, Čomić, Ljiljana R., Vasiljevic, Branka, Opsenica, Dejan, Milojković-Opsenica, Dušanka, Senerovic, Lidija, "Anti-quorum sensing activity, toxicity in zebrafish (Danio rerio) embryos and phytochemical characterization of Trapa natans leaf extracts" in Journal of Ethnopharmacology, 222 (2018):148-158,
https://doi.org/10.1016/j.jep.2018.05.005 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Šegan, Sandra
AU  - Andrić, Filip
AU  - Zlatović, Mario
AU  - Moric, Ivana
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2270
AB  - Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.
PB  - American Chemical Society (ACS)
T2  - Acs Chemical Biology
T1  - Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa
VL  - 12
IS  - 5
SP  - 1425
EP  - 1434
DO  - 10.1021/acschembio.6b01149
ER  - 

@article{
author = "Aleksić, Ivana and Šegan, Sandra and Andrić, Filip and Zlatović, Mario and Moric, Ivana and Opsenica, Dejan and Senerovic, Lidija",
year = "2017",
abstract = "Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Chemical Biology",
title = "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa",
volume = "12",
number = "5",
pages = "1425-1434",
doi = "10.1021/acschembio.6b01149"
}

Aleksić, I., Šegan, S., Andrić, F., Zlatović, M., Moric, I., Opsenica, D.,& Senerovic, L.. (2017). Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology
American Chemical Society (ACS)., 12(5), 1425-1434.
https://doi.org/10.1021/acschembio.6b01149

Aleksić I, Šegan S, Andrić F, Zlatović M, Moric I, Opsenica D, Senerovic L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology. 2017;12(5):1425-1434.
doi:10.1021/acschembio.6b01149 .

Aleksić, Ivana, Šegan, Sandra, Andrić, Filip, Zlatović, Mario, Moric, Ivana, Opsenica, Dejan, Senerovic, Lidija, "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa" in Acs Chemical Biology, 12, no. 5 (2017):1425-1434,
https://doi.org/10.1021/acschembio.6b01149 . .

TY  - JOUR
AU  - Aleksić, Ivana
AU  - Šegan, Sandra
AU  - Andrić, Filip
AU  - Zlatović, Mario
AU  - Moric, Ivana
AU  - Opsenica, Dejan
AU  - Senerovic, Lidija
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2983
AB  - Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.
PB  - American Chemical Society (ACS)
T2  - Acs Chemical Biology
T1  - Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa
VL  - 12
IS  - 5
SP  - 1425
EP  - 1434
DO  - 10.1021/acschembio.6b01149
ER  - 

@article{
author = "Aleksić, Ivana and Šegan, Sandra and Andrić, Filip and Zlatović, Mario and Moric, Ivana and Opsenica, Dejan and Senerovic, Lidija",
year = "2017",
abstract = "Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.",
publisher = "American Chemical Society (ACS)",
journal = "Acs Chemical Biology",
title = "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa",
volume = "12",
number = "5",
pages = "1425-1434",
doi = "10.1021/acschembio.6b01149"
}

Aleksić, I., Šegan, S., Andrić, F., Zlatović, M., Moric, I., Opsenica, D.,& Senerovic, L.. (2017). Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology
American Chemical Society (ACS)., 12(5), 1425-1434.
https://doi.org/10.1021/acschembio.6b01149

Aleksić I, Šegan S, Andrić F, Zlatović M, Moric I, Opsenica D, Senerovic L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology. 2017;12(5):1425-1434.
doi:10.1021/acschembio.6b01149 .

Aleksić, Ivana, Šegan, Sandra, Andrić, Filip, Zlatović, Mario, Moric, Ivana, Opsenica, Dejan, Senerovic, Lidija, "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa" in Acs Chemical Biology, 12, no. 5 (2017):1425-1434,
https://doi.org/10.1021/acschembio.6b01149 . .

TY  - JOUR
AU  - Dmitrović, Slavica
AU  - Škorić, Marijana
AU  - Boljević, Jelena
AU  - Aničić, Neda
AU  - Božić, Dragana
AU  - Mišić, Danijela
AU  - Filipović, Vuk
AU  - Opsenica, Dejan
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1892
AB  - The presented study aimed to investigate the elicitation possibility for the production of main secondary metabolites in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds belonging to tetraoxanes and thiophenes group. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenylthiophene) on the production of cis-trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on the culture medium with the addition of synthetic compounds in the concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and concentration of applied synthetic compounds. Application of DO63 in the concentration range 0.1-1 mg L-1 affected only NL production in both Nepeta species resulting in its increased content, while production of RA was not influenced in the treated shoots. Addition of DOVF15 caused decreased RA content in N. pannonica shoots and an increase in N. cataria shoots, whereas NL production was not affected. The presented results reveal the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species
VL  - 81
IS  - 9
SP  - 999
EP  - 1012
DO  - 10.2298/JSC160226054D
ER  - 

@article{
author = "Dmitrović, Slavica and Škorić, Marijana and Boljević, Jelena and Aničić, Neda and Božić, Dragana and Mišić, Danijela and Filipović, Vuk and Opsenica, Dejan",
year = "2016",
abstract = "The presented study aimed to investigate the elicitation possibility for the production of main secondary metabolites in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds belonging to tetraoxanes and thiophenes group. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenylthiophene) on the production of cis-trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on the culture medium with the addition of synthetic compounds in the concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and concentration of applied synthetic compounds. Application of DO63 in the concentration range 0.1-1 mg L-1 affected only NL production in both Nepeta species resulting in its increased content, while production of RA was not influenced in the treated shoots. Addition of DOVF15 caused decreased RA content in N. pannonica shoots and an increase in N. cataria shoots, whereas NL production was not affected. The presented results reveal the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species",
volume = "81",
number = "9",
pages = "999-1012",
doi = "10.2298/JSC160226054D"
}

Dmitrović, S., Škorić, M., Boljević, J., Aničić, N., Božić, D., Mišić, D., Filipović, V.,& Opsenica, D.. (2016). Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 81(9), 999-1012.
https://doi.org/10.2298/JSC160226054D

Dmitrović S, Škorić M, Boljević J, Aničić N, Božić D, Mišić D, Filipović V, Opsenica D. Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species. in Journal of the Serbian Chemical Society. 2016;81(9):999-1012.
doi:10.2298/JSC160226054D .

Dmitrović, Slavica, Škorić, Marijana, Boljević, Jelena, Aničić, Neda, Božić, Dragana, Mišić, Danijela, Filipović, Vuk, Opsenica, Dejan, "Elicitation effects of a synthetic 1,2,4,5-tetraoxane and a 2,5-diphenylthiophene in shoot cultures of two Nepeta species" in Journal of the Serbian Chemical Society, 81, no. 9 (2016):999-1012,
https://doi.org/10.2298/JSC160226054D . .

TY  - JOUR
AU  - Opsenica, Dejan
AU  - Radivojevic, Jelena
AU  - Matić, Ivana Z.
AU  - Štajner, Tijana
AU  - Knezevic-Usaj, Slavica
AU  - Djurkovic-Djakovic, Olgica
AU  - Šolaja, Bogdan
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1795
AB  - New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthesized and evaluated for their antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. The derivatives showed moderate, nM range antimalarial activities and low cytotoxicity. The N-phenylurea derivative 24 exhibited the best resistance indices (RIW2 = 0.44, RITM91C235 = 0.80) and was not toxic against human normal peripheral blood mononuclear cells (IC50 > 200 mu M). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukaemia K562 cells. One compound, derivative 21 with a primary amino group, was the first tetraoxane tested in vivo against Toxoplasma gondii as another apicomplexan parasite. Subcutaneous administration at a dose of 10 mg kg(-1) day(-1) for 8 days allowed the survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment of apicomplexan parasites.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules
VL  - 80
IS  - 11
SP  - 1339
DO  - 10.2298/JSC150430063O
ER  - 

@article{
author = "Opsenica, Dejan and Radivojevic, Jelena and Matić, Ivana Z. and Štajner, Tijana and Knezevic-Usaj, Slavica and Djurkovic-Djakovic, Olgica and Šolaja, Bogdan",
year = "2015",
abstract = "New cyclohexylidene 1,2,4,5-tetraoxanes with polar guanidine and urea based groups were synthesized and evaluated for their antimalarial activity against chloroquine resistant and susceptible Plasmodium falciparum strains. The derivatives showed moderate, nM range antimalarial activities and low cytotoxicity. The N-phenylurea derivative 24 exhibited the best resistance indices (RIW2 = 0.44, RITM91C235 = 0.80) and was not toxic against human normal peripheral blood mononuclear cells (IC50 > 200 mu M). Seven derivatives were tested in vitro against four human cancer cell lines and they demonstrated high selectivity toward leukaemia K562 cells. One compound, derivative 21 with a primary amino group, was the first tetraoxane tested in vivo against Toxoplasma gondii as another apicomplexan parasite. Subcutaneous administration at a dose of 10 mg kg(-1) day(-1) for 8 days allowed the survival of 20 % of infected mice, thus demonstrating the high potential of tetraoxanes for the treatment of apicomplexan parasites.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules",
volume = "80",
number = "11",
pages = "1339",
doi = "10.2298/JSC150430063O"
}

Opsenica, D., Radivojevic, J., Matić, I. Z., Štajner, T., Knezevic-Usaj, S., Djurkovic-Djakovic, O.,& Šolaja, B.. (2015). Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 80(11), 1339.
https://doi.org/10.2298/JSC150430063O

Opsenica D, Radivojevic J, Matić IZ, Štajner T, Knezevic-Usaj S, Djurkovic-Djakovic O, Šolaja B. Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules. in Journal of the Serbian Chemical Society. 2015;80(11):1339.
doi:10.2298/JSC150430063O .

Opsenica, Dejan, Radivojevic, Jelena, Matić, Ivana Z., Štajner, Tijana, Knezevic-Usaj, Slavica, Djurkovic-Djakovic, Olgica, Šolaja, Bogdan, "Tetraoxanes as inhibitors of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii growth and anti-cancer molecules" in Journal of the Serbian Chemical Society, 80, no. 11 (2015):1339,
https://doi.org/10.2298/JSC150430063O . .

TY  - JOUR
AU  - Nikolić, Stefan
AU  - Opsenica, Dejan
AU  - Filipović, Vuk
AU  - Dojčinović, Biljana
AU  - Arandelovic, Sandra
AU  - Radulovic, Singa
AU  - Grgurić-Šipka, Sanja
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1618
AB  - Two p-cymenerutheniumchlorido complexes with thiourea derivative of 7-chloroquinoline (C1) and pyridine-3-imidazole (C2) were synthesized starting from [(eta(6)-p-cymene)RuCl2](2) and corresponding ligands. The structures of complexes were determined with elemental analysis and IR, ESIMS, H-1 and C-13{H-1} NMR, and 2D H-1-N-15 correlation NMR spectroscopy. Cytotoxic activities examined by the MTT assay were performed in five human neoplastic cell lines (HeLa, K562, A549, MDA-MB-231, EA.hy926) and one nontumor human fetal lung fibroblast cell line (MRC-5). Tested complexes exhibited low micromolar activities with IC50 in the range 11.03-56.45 mu M, while ligands L1 and L2 were significantly less active. Complex C1 showed cytoselective activity toward the K562 cell line (IC50 = 11.03 +/- 1.39 mu M) and was 3 times less active against the nontumor MRC-5 cell line. Flow cytometry analysis indicated that complexes C1 and C2 after 24 h treatment caused a concentration-dependent increase of the apoptotic sub-G1 fraction (up to 18.4%), comparable to cis-diamminedichloridoplatinum(II) (cisplatin, CDDP), although without other substantial alterations of the cell cycle. A drug-accumulation and DNA-binding study performed by ICP-MS in the K562 cell line revealed that complex C1 had a high intracellular uptake (1.38 mu g Ru/10 (6) cells), which significantly exceeded the intracellular uptake levels of CDDP (0.29 mu g Pt/10 (6) cells) and C2 (0.08 mu g Ru/10 (6) cells). However, both ruthenium complexes C1 and C2 bind to cellular DNA less efficiently in comparison to CDDP. The structure-activity relationship clearly suggested that introduction of a 7-chloroquinoline moiety in the ruthenium(II)-p-cymene complex significantly contributed to the intracellular uptake of C1 and higher cytotoxicity and cytoselectivity.
PB  - American Chemical Society (ACS)
T2  - Organometallics
T1  - Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes
VL  - 34
IS  - 14
SP  - 3464
EP  - 3473
DO  - 10.1021/acs.organomet.5b00041
ER  - 

@article{
author = "Nikolić, Stefan and Opsenica, Dejan and Filipović, Vuk and Dojčinović, Biljana and Arandelovic, Sandra and Radulovic, Singa and Grgurić-Šipka, Sanja",
year = "2015",
abstract = "Two p-cymenerutheniumchlorido complexes with thiourea derivative of 7-chloroquinoline (C1) and pyridine-3-imidazole (C2) were synthesized starting from [(eta(6)-p-cymene)RuCl2](2) and corresponding ligands. The structures of complexes were determined with elemental analysis and IR, ESIMS, H-1 and C-13{H-1} NMR, and 2D H-1-N-15 correlation NMR spectroscopy. Cytotoxic activities examined by the MTT assay were performed in five human neoplastic cell lines (HeLa, K562, A549, MDA-MB-231, EA.hy926) and one nontumor human fetal lung fibroblast cell line (MRC-5). Tested complexes exhibited low micromolar activities with IC50 in the range 11.03-56.45 mu M, while ligands L1 and L2 were significantly less active. Complex C1 showed cytoselective activity toward the K562 cell line (IC50 = 11.03 +/- 1.39 mu M) and was 3 times less active against the nontumor MRC-5 cell line. Flow cytometry analysis indicated that complexes C1 and C2 after 24 h treatment caused a concentration-dependent increase of the apoptotic sub-G1 fraction (up to 18.4%), comparable to cis-diamminedichloridoplatinum(II) (cisplatin, CDDP), although without other substantial alterations of the cell cycle. A drug-accumulation and DNA-binding study performed by ICP-MS in the K562 cell line revealed that complex C1 had a high intracellular uptake (1.38 mu g Ru/10 (6) cells), which significantly exceeded the intracellular uptake levels of CDDP (0.29 mu g Pt/10 (6) cells) and C2 (0.08 mu g Ru/10 (6) cells). However, both ruthenium complexes C1 and C2 bind to cellular DNA less efficiently in comparison to CDDP. The structure-activity relationship clearly suggested that introduction of a 7-chloroquinoline moiety in the ruthenium(II)-p-cymene complex significantly contributed to the intracellular uptake of C1 and higher cytotoxicity and cytoselectivity.",
publisher = "American Chemical Society (ACS)",
journal = "Organometallics",
title = "Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes",
volume = "34",
number = "14",
pages = "3464-3473",
doi = "10.1021/acs.organomet.5b00041"
}

Nikolić, S., Opsenica, D., Filipović, V., Dojčinović, B., Arandelovic, S., Radulovic, S.,& Grgurić-Šipka, S.. (2015). Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes. in Organometallics
American Chemical Society (ACS)., 34(14), 3464-3473.
https://doi.org/10.1021/acs.organomet.5b00041

Nikolić S, Opsenica D, Filipović V, Dojčinović B, Arandelovic S, Radulovic S, Grgurić-Šipka S. Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes. in Organometallics. 2015;34(14):3464-3473.
doi:10.1021/acs.organomet.5b00041 .

Nikolić, Stefan, Opsenica, Dejan, Filipović, Vuk, Dojčinović, Biljana, Arandelovic, Sandra, Radulovic, Singa, Grgurić-Šipka, Sanja, "Strong in Vitro Cytotoxic Potential of New Ruthenium-Cymene Complexes" in Organometallics, 34, no. 14 (2015):3464-3473,
https://doi.org/10.1021/acs.organomet.5b00041 . .

TY  - JOUR
AU  - Videnović, Milica
AU  - Opsenica, Dejan
AU  - Burnett, James C.
AU  - Gomba, Laura
AU  - Nuss, Jonathan E.
AU  - Selaković, Života
AU  - Konstantinović, Jelena M.
AU  - Krstic, Maja
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Sciotti, Richard J.
AU  - Bavari, Sina
AU  - Šolaja, Bogdan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1580
AB  - Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.
PB  - American Chemical Society (ACS)
T2  - Journal of Medicinal Chemistry
T1  - Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria
VL  - 57
IS  - 10
SP  - 4134
EP  - 4153
DO  - 10.1021/jm500033r
ER  - 

@article{
author = "Videnović, Milica and Opsenica, Dejan and Burnett, James C. and Gomba, Laura and Nuss, Jonathan E. and Selaković, Života and Konstantinović, Jelena M. and Krstic, Maja and Šegan, Sandra and Zlatović, Mario and Sciotti, Richard J. and Bavari, Sina and Šolaja, Bogdan",
year = "2014",
abstract = "Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of Medicinal Chemistry",
title = "Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria",
volume = "57",
number = "10",
pages = "4134-4153",
doi = "10.1021/jm500033r"
}

Videnović, M., Opsenica, D., Burnett, J. C., Gomba, L., Nuss, J. E., Selaković, Ž., Konstantinović, J. M., Krstic, M., Šegan, S., Zlatović, M., Sciotti, R. J., Bavari, S.,& Šolaja, B.. (2014). Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria. in Journal of Medicinal Chemistry
American Chemical Society (ACS)., 57(10), 4134-4153.
https://doi.org/10.1021/jm500033r

Videnović M, Opsenica D, Burnett JC, Gomba L, Nuss JE, Selaković Ž, Konstantinović JM, Krstic M, Šegan S, Zlatović M, Sciotti RJ, Bavari S, Šolaja B. Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria. in Journal of Medicinal Chemistry. 2014;57(10):4134-4153.
doi:10.1021/jm500033r .

Videnović, Milica, Opsenica, Dejan, Burnett, James C., Gomba, Laura, Nuss, Jonathan E., Selaković, Života, Konstantinović, Jelena M., Krstic, Maja, Šegan, Sandra, Zlatović, Mario, Sciotti, Richard J., Bavari, Sina, Šolaja, Bogdan, "Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria" in Journal of Medicinal Chemistry, 57, no. 10 (2014):4134-4153,
https://doi.org/10.1021/jm500033r . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Terzić Jovanović, Nataša
AU  - Milojković-Opsenica, Dušanka
AU  - Trifković, Jelena
AU  - Šolaja, Bogdan
AU  - Opsenica, Dejan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1599
AB  - The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic acid derivatives with distinct biological activity, was examined by high-performance thin-layer chromatography in order to correlate their structure and retention. Chromatographic systems were consisted of RP-18 or CN-silica as stationary phase, and binary mixtures of water with methanol, dioxane or acetone as mobile phase. Based on the respective retentions, the lipophilicity of the investigated compounds was determined. Multiple linear regression and partial least squares have been used to select variables that best describe the behavior of the investigated compounds in chromatographic systems and to quantify influences of most important parameters. The validation and cross-validation of the QSRR model suggest its applicability for prediction and understanding of retention of congeners. The models indicate the importance of nonpolar properties of the solutes and their ability for hydrophobic interactions, as well as the importance of proton donating abilities, hydrophilic and,pi interactions pointing out on that way the possible separation mechanism in the studied chromatographic systems. Observed correlations between structure and biological activity of mixed 1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6 Plasmodium falciparum strains, is governed by hydrophobic feature (measured with lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA descriptors), and electronic feature (HOMO).
PB  - Elsevier
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters
VL  - 97
SP  - 178
EP  - 183
DO  - 10.1016/j.jpba.2014.04.029
ER  - 

@article{
author = "Šegan, Sandra and Terzić Jovanović, Nataša and Milojković-Opsenica, Dušanka and Trifković, Jelena and Šolaja, Bogdan and Opsenica, Dejan",
year = "2014",
abstract = "The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic acid derivatives with distinct biological activity, was examined by high-performance thin-layer chromatography in order to correlate their structure and retention. Chromatographic systems were consisted of RP-18 or CN-silica as stationary phase, and binary mixtures of water with methanol, dioxane or acetone as mobile phase. Based on the respective retentions, the lipophilicity of the investigated compounds was determined. Multiple linear regression and partial least squares have been used to select variables that best describe the behavior of the investigated compounds in chromatographic systems and to quantify influences of most important parameters. The validation and cross-validation of the QSRR model suggest its applicability for prediction and understanding of retention of congeners. The models indicate the importance of nonpolar properties of the solutes and their ability for hydrophobic interactions, as well as the importance of proton donating abilities, hydrophilic and,pi interactions pointing out on that way the possible separation mechanism in the studied chromatographic systems. Observed correlations between structure and biological activity of mixed 1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6 Plasmodium falciparum strains, is governed by hydrophobic feature (measured with lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA descriptors), and electronic feature (HOMO).",
publisher = "Elsevier",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters",
volume = "97",
pages = "178-183",
doi = "10.1016/j.jpba.2014.04.029"
}

Šegan, S., Terzić Jovanović, N., Milojković-Opsenica, D., Trifković, J., Šolaja, B.,& Opsenica, D.. (2014). Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier., 97, 178-183.
https://doi.org/10.1016/j.jpba.2014.04.029

Šegan S, Terzić Jovanović N, Milojković-Opsenica D, Trifković J, Šolaja B, Opsenica D. Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters. in Journal of Pharmaceutical and Biomedical Analysis. 2014;97:178-183.
doi:10.1016/j.jpba.2014.04.029 .

Šegan, Sandra, Terzić Jovanović, Nataša, Milojković-Opsenica, Dušanka, Trifković, Jelena, Šolaja, Bogdan, Opsenica, Dejan, "Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters" in Journal of Pharmaceutical and Biomedical Analysis, 97 (2014):178-183,
https://doi.org/10.1016/j.jpba.2014.04.029 . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Terzić-Jovanović, Nataša
AU  - Milojković-Opsenica, Dušanka
AU  - Trifković, Jelena
AU  - Šolaja, Bogdan
AU  - Opsenica, Dejan
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3166
AB  - The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic acid derivatives with distinct biological activity, was examined by high-performance thin-layer chromatography in order to correlate their structure and retention. Chromatographic systems were consisted of RP-18 or CN-silica as stationary phase, and binary mixtures of water with methanol, dioxane or acetone as mobile phase. Based on the respective retentions, the lipophilicity of the investigated compounds was determined. Multiple linear regression and partial least squares have been used to select variables that best describe the behavior of the investigated compounds in chromatographic systems and to quantify influences of most important parameters. The validation and cross-validation of the QSRR model suggest its applicability for prediction and understanding of retention of congeners. The models indicate the importance of nonpolar properties of the solutes and their ability for hydrophobic interactions, as well as the importance of proton donating abilities, hydrophilic and,pi interactions pointing out on that way the possible separation mechanism in the studied chromatographic systems. Observed correlations between structure and biological activity of mixed 1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6 Plasmodium falciparum strains, is governed by hydrophobic feature (measured with lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA descriptors), and electronic feature (HOMO).
PB  - Elsevier
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters
VL  - 97
SP  - 178
EP  - 183
DO  - 10.1016/j.jpba.2014.04.029
ER  - 

@article{
author = "Šegan, Sandra and Terzić-Jovanović, Nataša and Milojković-Opsenica, Dušanka and Trifković, Jelena and Šolaja, Bogdan and Opsenica, Dejan",
year = "2014",
abstract = "The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic acid derivatives with distinct biological activity, was examined by high-performance thin-layer chromatography in order to correlate their structure and retention. Chromatographic systems were consisted of RP-18 or CN-silica as stationary phase, and binary mixtures of water with methanol, dioxane or acetone as mobile phase. Based on the respective retentions, the lipophilicity of the investigated compounds was determined. Multiple linear regression and partial least squares have been used to select variables that best describe the behavior of the investigated compounds in chromatographic systems and to quantify influences of most important parameters. The validation and cross-validation of the QSRR model suggest its applicability for prediction and understanding of retention of congeners. The models indicate the importance of nonpolar properties of the solutes and their ability for hydrophobic interactions, as well as the importance of proton donating abilities, hydrophilic and,pi interactions pointing out on that way the possible separation mechanism in the studied chromatographic systems. Observed correlations between structure and biological activity of mixed 1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6 Plasmodium falciparum strains, is governed by hydrophobic feature (measured with lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA descriptors), and electronic feature (HOMO).",
publisher = "Elsevier",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters",
volume = "97",
pages = "178-183",
doi = "10.1016/j.jpba.2014.04.029"
}

Šegan, S., Terzić-Jovanović, N., Milojković-Opsenica, D., Trifković, J., Šolaja, B.,& Opsenica, D.. (2014). Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier., 97, 178-183.
https://doi.org/10.1016/j.jpba.2014.04.029

Šegan S, Terzić-Jovanović N, Milojković-Opsenica D, Trifković J, Šolaja B, Opsenica D. Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters. in Journal of Pharmaceutical and Biomedical Analysis. 2014;97:178-183.
doi:10.1016/j.jpba.2014.04.029 .

Šegan, Sandra, Terzić-Jovanović, Nataša, Milojković-Opsenica, Dušanka, Trifković, Jelena, Šolaja, Bogdan, Opsenica, Dejan, "Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters" in Journal of Pharmaceutical and Biomedical Analysis, 97 (2014):178-183,
https://doi.org/10.1016/j.jpba.2014.04.029 . .

TY  - JOUR
AU  - Reljic, Zorica
AU  - Zlatović, Mario
AU  - Savic-Radojevic, Ana
AU  - Pekmezovic, Tatjana
AU  - Djukanovic, Ljubica
AU  - Matic, Marija
AU  - Pljesa-Ercegovac, Marija
AU  - Mimic-Oka, Jasmina
AU  - Opsenica, Dejan
AU  - Simić, Tatjana
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1417
AB  - Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.
PB  - MDPI
T2  - Toxins
T1  - Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis
VL  - 6
IS  - 8
SP  - 2348
EP  - 2362
DO  - 10.3390/toxins6082348
ER  - 

@article{
author = "Reljic, Zorica and Zlatović, Mario and Savic-Radojevic, Ana and Pekmezovic, Tatjana and Djukanovic, Ljubica and Matic, Marija and Pljesa-Ercegovac, Marija and Mimic-Oka, Jasmina and Opsenica, Dejan and Simić, Tatjana",
year = "2014",
abstract = "Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates.",
publisher = "MDPI",
journal = "Toxins",
title = "Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis",
volume = "6",
number = "8",
pages = "2348-2362",
doi = "10.3390/toxins6082348"
}

Reljic, Z., Zlatović, M., Savic-Radojevic, A., Pekmezovic, T., Djukanovic, L., Matic, M., Pljesa-Ercegovac, M., Mimic-Oka, J., Opsenica, D.,& Simić, T.. (2014). Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis. in Toxins
MDPI., 6(8), 2348-2362.
https://doi.org/10.3390/toxins6082348

Reljic Z, Zlatović M, Savic-Radojevic A, Pekmezovic T, Djukanovic L, Matic M, Pljesa-Ercegovac M, Mimic-Oka J, Opsenica D, Simić T. Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis. in Toxins. 2014;6(8):2348-2362.
doi:10.3390/toxins6082348 .

Reljic, Zorica, Zlatović, Mario, Savic-Radojevic, Ana, Pekmezovic, Tatjana, Djukanovic, Ljubica, Matic, Marija, Pljesa-Ercegovac, Marija, Mimic-Oka, Jasmina, Opsenica, Dejan, Simić, Tatjana, "Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis" in Toxins, 6, no. 8 (2014):2348-2362,
https://doi.org/10.3390/toxins6082348 . .