TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Dukić-Stefanović, Sladjana
AU  - Deuther-Conrad, Winnie
AU  - Andrić, Deana
AU  - Kostić-Rajačić, Slađana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5830
AB  - Serotonin receptors modulate numerous behavioral and neuropsychological processes.
Therefore, they are the target for the action of many drugs, such as antipsychotics, antidepressants,
antiemetics, migraine remedies, and many others. The 5-HT1A receptors have been involved in the
pathogenesis and treatment of anxiety and depression and represent a promising target for new
drugs with reduced extrapyramidal side effects. In most antidepressants, a piperazine-based structural
motif can be identified as a common moiety. Here we describe the synthesis, pharmacological,
and in silico characterization of a novel arylpiperazines series with excellent 5-HT1A affinity. The
final compounds, 4a, 8a, and 8b, were selected according to predictions of in silico pharmacokinetics,
docking analysis, and molecular dynamics in conjunction with physical properties, and metabolic
stability. The accentuated molecules could serve as a lead compound for developing 5-
HT1A drug-like molecules for depression treatment.
PB  - Elsevier
T2  - Arabian Journal of Chemistry
T1  - Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency
VL  - 16
IS  - 4
SP  - 104636
DO  - 10.1016/j.arabjc.2023.104636
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Dukić-Stefanović, Sladjana and Deuther-Conrad, Winnie and Andrić, Deana and Kostić-Rajačić, Slađana",
year = "2023",
abstract = "Serotonin receptors modulate numerous behavioral and neuropsychological processes.
Therefore, they are the target for the action of many drugs, such as antipsychotics, antidepressants,
antiemetics, migraine remedies, and many others. The 5-HT1A receptors have been involved in the
pathogenesis and treatment of anxiety and depression and represent a promising target for new
drugs with reduced extrapyramidal side effects. In most antidepressants, a piperazine-based structural
motif can be identified as a common moiety. Here we describe the synthesis, pharmacological,
and in silico characterization of a novel arylpiperazines series with excellent 5-HT1A affinity. The
final compounds, 4a, 8a, and 8b, were selected according to predictions of in silico pharmacokinetics,
docking analysis, and molecular dynamics in conjunction with physical properties, and metabolic
stability. The accentuated molecules could serve as a lead compound for developing 5-
HT1A drug-like molecules for depression treatment.",
publisher = "Elsevier",
journal = "Arabian Journal of Chemistry",
title = "Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency",
volume = "16",
number = "4",
pages = "104636",
doi = "10.1016/j.arabjc.2023.104636"
}

Penjišević, J., Šukalović, V., Dukić-Stefanović, S., Deuther-Conrad, W., Andrić, D.,& Kostić-Rajačić, S.. (2023). Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency. in Arabian Journal of Chemistry
Elsevier., 16(4), 104636.
https://doi.org/10.1016/j.arabjc.2023.104636

Penjišević J, Šukalović V, Dukić-Stefanović S, Deuther-Conrad W, Andrić D, Kostić-Rajačić S. Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency. in Arabian Journal of Chemistry. 2023;16(4):104636.
doi:10.1016/j.arabjc.2023.104636 .

Penjišević, Jelena, Šukalović, Vladimir, Dukić-Stefanović, Sladjana, Deuther-Conrad, Winnie, Andrić, Deana, Kostić-Rajačić, Slađana, "Synthesis of novel 5-HT1A arylpiperazine ligands: Binding data and computer-aided analysis of pharmacological potency" in Arabian Journal of Chemistry, 16, no. 4 (2023):104636,
https://doi.org/10.1016/j.arabjc.2023.104636 . .

TY  - JOUR
AU  - Krunić, Mihajlo
AU  - Penjišević, Jelena
AU  - Suručić, Relja
AU  - Šegan, Sandra
AU  - Kostić-Rajačić, Slađana
AU  - Jevtić, Ivana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5634
AB  - Fourteen novel N-benzylpiperidine and N,N-diarylpiperazine conjugates were synthesized and pharmacologically evaluated as donepezil analogs, in a ligand-based drug design approach. All compounds possessed high to moderate in vitro inhibitory activity with IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type mode of inhibition, binding to both, free enzyme and enzyme-substrate complex. For further understanding of mechanism of action and binding orientations, molecular docking was performed for all compounds, while the ligand transport simulation and molecular dynamics simulations were performed for 7g and 8g. Computational results corroborated well with in vitro activities and kinetic studies.
PB  - Elsevier B.V.
T2  - Journal of Molecular Structure
T1  - Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors
VL  - 1276
SP  - 134809
DO  - 10.1016/j.molstruc.2022.134809
ER  - 

@article{
author = "Krunić, Mihajlo and Penjišević, Jelena and Suručić, Relja and Šegan, Sandra and Kostić-Rajačić, Slađana and Jevtić, Ivana",
year = "2023",
abstract = "Fourteen novel N-benzylpiperidine and N,N-diarylpiperazine conjugates were synthesized and pharmacologically evaluated as donepezil analogs, in a ligand-based drug design approach. All compounds possessed high to moderate in vitro inhibitory activity with IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type mode of inhibition, binding to both, free enzyme and enzyme-substrate complex. For further understanding of mechanism of action and binding orientations, molecular docking was performed for all compounds, while the ligand transport simulation and molecular dynamics simulations were performed for 7g and 8g. Computational results corroborated well with in vitro activities and kinetic studies.",
publisher = "Elsevier B.V.",
journal = "Journal of Molecular Structure",
title = "Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors",
volume = "1276",
pages = "134809",
doi = "10.1016/j.molstruc.2022.134809"
}

Krunić, M., Penjišević, J., Suručić, R., Šegan, S., Kostić-Rajačić, S.,& Jevtić, I.. (2023). Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors. in Journal of Molecular Structure
Elsevier B.V.., 1276, 134809.
https://doi.org/10.1016/j.molstruc.2022.134809

Krunić M, Penjišević J, Suručić R, Šegan S, Kostić-Rajačić S, Jevtić I. Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors. in Journal of Molecular Structure. 2023;1276:134809.
doi:10.1016/j.molstruc.2022.134809 .

Krunić, Mihajlo, Penjišević, Jelena, Suručić, Relja, Šegan, Sandra, Kostić-Rajačić, Slađana, Jevtić, Ivana, "Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors" in Journal of Molecular Structure, 1276 (2023):134809,
https://doi.org/10.1016/j.molstruc.2022.134809 . .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Suručić, Relja
AU  - Kostić Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5229
AB  - Adrenergic receptors are among the most studied G protein-coupled receptors. Activation or blockade of these receptors is a major therapeutic approach for the treatment of numerous disorders such as cardiac hypertrophy, congestive heart failure, hypertension, angina pectoris, cardiac arrhythmias, depression, benign prostate hyperplasia, anaphylaxis, asthma, and hyperthyroidism. Among all nine cloned adrenoceptor subtypes and the subsequent development of animal models, a significant target for various neurological conditions treatment is alpha1-adrenergic receptors. 2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. Most of the novel compounds showed alpha1-adrenergic affinity in the range from 22 nM to 250 nM. The in silico docking and molecular dynamics simulations, binding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists.
PB  - Springer
T2  - Applied Biochemistry and Biotechnology
T1  - The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study
VL  - 194
SP  - 3749
EP  - 3764
DO  - 10.1007/s12010-022-03922-8
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Suručić, Relja and Kostić Rajačić, Slađana",
year = "2022",
abstract = "Adrenergic receptors are among the most studied G protein-coupled receptors. Activation or blockade of these receptors is a major therapeutic approach for the treatment of numerous disorders such as cardiac hypertrophy, congestive heart failure, hypertension, angina pectoris, cardiac arrhythmias, depression, benign prostate hyperplasia, anaphylaxis, asthma, and hyperthyroidism. Among all nine cloned adrenoceptor subtypes and the subsequent development of animal models, a significant target for various neurological conditions treatment is alpha1-adrenergic receptors. 2-{[4-(2-Methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles, their 5 substituted derivatives, and structurally similar, arylpiperazine based alpha1-adrenergic receptors antagonists (trazodone, naftopidil, and urapidil) have been subjects of comparative analysis. Most of the novel compounds showed alpha1-adrenergic affinity in the range from 22 nM to 250 nM. The in silico docking and molecular dynamics simulations, binding data together with absorption, distribution, metabolism, and excretion (ADME) calculations identified the promising lead compounds. The results brought out the conclusions which allowed us to propose a rationale for the activity of these molecules and to highlight six compounds (2-5, 8, and 12) that exhibited an acceptable pharmacokinetic profile to the advanced investigation as the potential alpha1-adrenergic receptor antagonists.",
publisher = "Springer",
journal = "Applied Biochemistry and Biotechnology",
title = "The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study",
volume = "194",
pages = "3749-3764",
doi = "10.1007/s12010-022-03922-8"
}

Penjišević, J., Šukalović, V., Andrić, D., Suručić, R.,& Kostić Rajačić, S.. (2022). The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study. in Applied Biochemistry and Biotechnology
Springer., 194, 3749-3764.
https://doi.org/10.1007/s12010-022-03922-8

Penjišević J, Šukalović V, Andrić D, Suručić R, Kostić Rajačić S. The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study. in Applied Biochemistry and Biotechnology. 2022;194:3749-3764.
doi:10.1007/s12010-022-03922-8 .

Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Suručić, Relja, Kostić Rajačić, Slađana, "The Therapeutic Potential of 2-{[4-(2-methoxyphenyl)piperazin-1-yl]alkyl}-1H-benzo[d]imidazoles as Ligands for Alpha1-Adrenergic Receptor - Comparative In Silico and In Vitro Study" in Applied Biochemistry and Biotechnology, 194 (2022):3749-3764,
https://doi.org/10.1007/s12010-022-03922-8 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Dukic-Stefanovic, Sladjana
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5851
AB  - Serotonin 5HT1a receptors belongs to a class G-protein coupled receptors and it is widely recognized as one of the targets for treating neurological disorders such depression and schizophrenia. N-arylpiperazine structural motif is present in many compounds with pronounced 5HT1a activity including recently approved aripiprazole for the treatment of the major depressive disorder.
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
T1  - Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_cer_5851
ER  - 

@conference{
author = "Jevtić, Ivana and Andrić, Deana and Penjišević, Jelena and Šukalović, Vladimir and Dukic-Stefanovic, Sladjana and Kostić-Rajačić, Slađana",
year = "2022",
abstract = "Serotonin 5HT1a receptors belongs to a class G-protein coupled receptors and it is widely recognized as one of the targets for treating neurological disorders such depression and schizophrenia. N-arylpiperazine structural motif is present in many compounds with pronounced 5HT1a activity including recently approved aripiprazole for the treatment of the major depressive disorder.",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France",
title = "Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_cer_5851"
}

Jevtić, I., Andrić, D., Penjišević, J., Šukalović, V., Dukic-Stefanovic, S.,& Kostić-Rajačić, S.. (2022). Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
European Federation for Medicinal chemistry and Chemical biology (EFMC)., 66-66.
https://hdl.handle.net/21.15107/rcub_cer_5851

Jevtić I, Andrić D, Penjišević J, Šukalović V, Dukic-Stefanovic S, Kostić-Rajačić S. Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France. 2022;:66-66.
https://hdl.handle.net/21.15107/rcub_cer_5851 .

Jevtić, Ivana, Andrić, Deana, Penjišević, Jelena, Šukalović, Vladimir, Dukic-Stefanovic, Sladjana, Kostić-Rajačić, Slađana, "Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands" in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France (2022):66-66,
https://hdl.handle.net/21.15107/rcub_cer_5851 .

TY  - CONF
AU  - Krunić, Mihajlo
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5850
AB  - Alzheimer's disease (AD) is a serious, neurodegenerative disease, characterized with a progressive loss of cognitive and behavioral functions leading to fatal outcome. Tacrine belongs to a class of cholinesterase inhibitors(ChEls) and it is the first ChEI marketed for the treatment of AD symptoms.
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
T1  - Novel multitarget tacrine derivatives: design and structure activity relationship
SP  - P013
UR  - https://hdl.handle.net/21.15107/rcub_cer_5850
ER  - 

@conference{
author = "Krunić, Mihajlo and Jevtić, Ivana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2022",
abstract = "Alzheimer's disease (AD) is a serious, neurodegenerative disease, characterized with a progressive loss of cognitive and behavioral functions leading to fatal outcome. Tacrine belongs to a class of cholinesterase inhibitors(ChEls) and it is the first ChEI marketed for the treatment of AD symptoms.",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France",
title = "Novel multitarget tacrine derivatives: design and structure activity relationship",
pages = "P013",
url = "https://hdl.handle.net/21.15107/rcub_cer_5850"
}

Krunić, M., Jevtić, I., Penjišević, J.,& Kostić-Rajačić, S.. (2022). Novel multitarget tacrine derivatives: design and structure activity relationship. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
European Federation for Medicinal chemistry and Chemical biology (EFMC)., P013.
https://hdl.handle.net/21.15107/rcub_cer_5850

Krunić M, Jevtić I, Penjišević J, Kostić-Rajačić S. Novel multitarget tacrine derivatives: design and structure activity relationship. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France. 2022;:P013.
https://hdl.handle.net/21.15107/rcub_cer_5850 .

Krunić, Mihajlo, Jevtić, Ivana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Novel multitarget tacrine derivatives: design and structure activity relationship" in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France (2022):P013,
https://hdl.handle.net/21.15107/rcub_cer_5850 .

TY  - JOUR
AU  - Krunić, Mihajlo
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4972
AB  - The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald– Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning.
AB  - У овом раду представљена је синтеза новог трицикличног система који садржи азот.  Три нова једињења код којих су комбиноване структурне карактеристике 1,2,3,4-тетрахидрохиноксалина и декахидропиридо[3,4-b]пиразина, добијена су полазећи од лако доступних прекурсора, у шест или седам фаза од којих су последње три или четири,  редом, диастереоселективне. Кључне синтетичке трансформације укључују N-ациловање, Hofmann премештање и интрамолекулску Buchwald–Hartwig реакцију, као фазу у којој долази до циклизације. Једињења trans-8, cis-12 и trans-12 су синтетисана како би се представила могућност функционализације новог трицикличног система. Синтетички значај новог хетероцикличног система представљен је у могућности ортогоналне функционализације три различите амино групе, чиме се може постићи фино подешавање структуре.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system
T1  - Синтетски пут за добијање 1,2,3,4-тетрахидрохиноксалинскo/пиперидинског трицикличног система
VL  - 87
IS  - 2
SP  - 169
EP  - 179
DO  - 10.2298/JSC210416068K
ER  - 

@article{
author = "Krunić, Mihajlo and Jevtić, Ivana and Penjišević, Jelena and Kostić Rajačić, Slađana",
year = "2022",
abstract = "The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald– Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning., У овом раду представљена је синтеза новог трицикличног система који садржи азот.  Три нова једињења код којих су комбиноване структурне карактеристике 1,2,3,4-тетрахидрохиноксалина и декахидропиридо[3,4-b]пиразина, добијена су полазећи од лако доступних прекурсора, у шест или седам фаза од којих су последње три или четири,  редом, диастереоселективне. Кључне синтетичке трансформације укључују N-ациловање, Hofmann премештање и интрамолекулску Buchwald–Hartwig реакцију, као фазу у којој долази до циклизације. Једињења trans-8, cis-12 и trans-12 су синтетисана како би се представила могућност функционализације новог трицикличног система. Синтетички значај новог хетероцикличног система представљен је у могућности ортогоналне функционализације три различите амино групе, чиме се може постићи фино подешавање структуре.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system, Синтетски пут за добијање 1,2,3,4-тетрахидрохиноксалинскo/пиперидинског трицикличног система",
volume = "87",
number = "2",
pages = "169-179",
doi = "10.2298/JSC210416068K"
}

Krunić, M., Jevtić, I., Penjišević, J.,& Kostić Rajačić, S.. (2022). Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 87(2), 169-179.
https://doi.org/10.2298/JSC210416068K

Krunić M, Jevtić I, Penjišević J, Kostić Rajačić S. Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system. in Journal of the Serbian Chemical Society. 2022;87(2):169-179.
doi:10.2298/JSC210416068K .

Krunić, Mihajlo, Jevtić, Ivana, Penjišević, Jelena, Kostić Rajačić, Slađana, "Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system" in Journal of the Serbian Chemical Society, 87, no. 2 (2022):169-179,
https://doi.org/10.2298/JSC210416068K . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Jevtić, Ivana
AU  - Tosti, Tomislav
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Kostić Rajačić, Slađana
AU  - Milojković-Opsenica, Dušanka
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5413
AB  - Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.
PB  - Elsevier
T2  - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
T1  - Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography
VL  - 1211
SP  - 123481
DO  - 10.1016/j.jchromb.2022.123481
ER  - 

@article{
author = "Šegan, Sandra and Jevtić, Ivana and Tosti, Tomislav and Penjišević, Jelena and Šukalović, Vladimir and Kostić Rajačić, Slađana and Milojković-Opsenica, Dušanka",
year = "2022",
abstract = "Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.",
publisher = "Elsevier",
journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences",
title = "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography",
volume = "1211",
pages = "123481",
doi = "10.1016/j.jchromb.2022.123481"
}

Šegan, S., Jevtić, I., Tosti, T., Penjišević, J., Šukalović, V., Kostić Rajačić, S.,& Milojković-Opsenica, D.. (2022). Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Elsevier., 1211, 123481.
https://doi.org/10.1016/j.jchromb.2022.123481

Šegan S, Jevtić I, Tosti T, Penjišević J, Šukalović V, Kostić Rajačić S, Milojković-Opsenica D. Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2022;1211:123481.
doi:10.1016/j.jchromb.2022.123481 .

Šegan, Sandra, Jevtić, Ivana, Tosti, Tomislav, Penjišević, Jelena, Šukalović, Vladimir, Kostić Rajačić, Slađana, Milojković-Opsenica, Dušanka, "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography" in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1211 (2022):123481,
https://doi.org/10.1016/j.jchromb.2022.123481 . .

TY  - CONF
AU  - Andrić, Deana
AU  - Dukic-Stefanovic, Sladjana
AU  - Penjišević, Jelena
AU  - Jevtić, Ivana
AU  - Šukalović, Vladimir
AU  - Suručić, Relja
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5849
AB  - 5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric
disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of
new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand
aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations,
revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine
selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro
pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c)
with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM,
respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c
possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological
results are therefore in accordance with the molecular docking simulations thus proving the rational
design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new,
potential antidepressants.
PB  - Kragujevac : Institute for Information Technologies
C3  - Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac
T1  - Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
SP  - 355
EP  - 358
DO  - 10.46793/ICCBI21.355A
ER  - 

@conference{
author = "Andrić, Deana and Dukic-Stefanovic, Sladjana and Penjišević, Jelena and Jevtić, Ivana and Šukalović, Vladimir and Suručić, Relja and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric
disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of
new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand
aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations,
revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine
selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro
pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c)
with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM,
respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c
possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological
results are therefore in accordance with the molecular docking simulations thus proving the rational
design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new,
potential antidepressants.",
publisher = "Kragujevac : Institute for Information Technologies",
journal = "Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac",
title = "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides",
pages = "355-358",
doi = "10.46793/ICCBI21.355A"
}

Andrić, D., Dukic-Stefanovic, S., Penjišević, J., Jevtić, I., Šukalović, V., Suručić, R.,& Kostić-Rajačić, S.. (2021). Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac
Kragujevac : Institute for Information Technologies., 355-358.
https://doi.org/10.46793/ICCBI21.355A

Andrić D, Dukic-Stefanovic S, Penjišević J, Jevtić I, Šukalović V, Suručić R, Kostić-Rajačić S. Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac. 2021;:355-358.
doi:10.46793/ICCBI21.355A .

Andrić, Deana, Dukic-Stefanovic, Sladjana, Penjišević, Jelena, Jevtić, Ivana, Šukalović, Vladimir, Suručić, Relja, Kostić-Rajačić, Slađana, "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac (2021):355-358,
https://doi.org/10.46793/ICCBI21.355A . .

TY  - JOUR
AU  - Dukić-Stefanović, Sladjana
AU  - Lai, Thu Hang
AU  - Toussaint, Magali
AU  - Clauß, Oliver
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Ludwig, Friedrich-Alexander
AU  - Gündel, Daniel
AU  - Deuther-Conrad, Winnie
AU  - Kostić Rajačić, Slađana
AU  - Brust, Peter
AU  - Teodoro, Rodrigo
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4756
AB  - Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.
PB  - Elsevier
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain
VL  - 48
SP  - 128254
DO  - 10.1016/j.bmcl.2021.128254
ER  - 

@article{
author = "Dukić-Stefanović, Sladjana and Lai, Thu Hang and Toussaint, Magali and Clauß, Oliver and Jevtić, Ivana and Penjišević, Jelena and Andrić, Deana and Ludwig, Friedrich-Alexander and Gündel, Daniel and Deuther-Conrad, Winnie and Kostić Rajačić, Slađana and Brust, Peter and Teodoro, Rodrigo",
year = "2021",
abstract = "Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.",
publisher = "Elsevier",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain",
volume = "48",
pages = "128254",
doi = "10.1016/j.bmcl.2021.128254"
}

Dukić-Stefanović, S., Lai, T. H., Toussaint, M., Clauß, O., Jevtić, I., Penjišević, J., Andrić, D., Ludwig, F., Gündel, D., Deuther-Conrad, W., Kostić Rajačić, S., Brust, P.,& Teodoro, R.. (2021). In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters
Elsevier., 48, 128254.
https://doi.org/10.1016/j.bmcl.2021.128254

Dukić-Stefanović S, Lai TH, Toussaint M, Clauß O, Jevtić I, Penjišević J, Andrić D, Ludwig F, Gündel D, Deuther-Conrad W, Kostić Rajačić S, Brust P, Teodoro R. In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters. 2021;48:128254.
doi:10.1016/j.bmcl.2021.128254 .

Dukić-Stefanović, Sladjana, Lai, Thu Hang, Toussaint, Magali, Clauß, Oliver, Jevtić, Ivana, Penjišević, Jelena, Andrić, Deana, Ludwig, Friedrich-Alexander, Gündel, Daniel, Deuther-Conrad, Winnie, Kostić Rajačić, Slađana, Brust, Peter, Teodoro, Rodrigo, "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain" in Bioorganic and Medicinal Chemistry Letters, 48 (2021):128254,
https://doi.org/10.1016/j.bmcl.2021.128254 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5837
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by deterioration of
cognitive skills and it is the most abundant form of dementia according to the World Health Organization
(WHO).1 Tacrine belongs to a class of acetylcholinesterase inhibitors (AChEIs) and it was formerly used in the
treatment of AD symptoms. Albeit no longer in clinical use due to its hepatotoxicity, tacrine ring system is
extensively investigated as pharmacophore in novel AChEIs, many of which showed improved pharmacological
profile in the preclinical studies.2 Here we present optimized synthetic pathway and pharmacological evaluation
of three novel tacrine derivatives (5, 6 and 7), possessing functionalized piperidine connected with tacrine via
five methylene groups alkyl chain
PB  - The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society
C3  - Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event
T1  - Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors
SP  - 119
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_cer_5837
ER  - 

@conference{
author = "Jevtić, Ivana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by deterioration of
cognitive skills and it is the most abundant form of dementia according to the World Health Organization
(WHO).1 Tacrine belongs to a class of acetylcholinesterase inhibitors (AChEIs) and it was formerly used in the
treatment of AD symptoms. Albeit no longer in clinical use due to its hepatotoxicity, tacrine ring system is
extensively investigated as pharmacophore in novel AChEIs, many of which showed improved pharmacological
profile in the preclinical studies.2 Here we present optimized synthetic pathway and pharmacological evaluation
of three novel tacrine derivatives (5, 6 and 7), possessing functionalized piperidine connected with tacrine via
five methylene groups alkyl chain",
publisher = "The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society",
journal = "Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event",
title = "Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors",
pages = "119-119",
url = "https://hdl.handle.net/21.15107/rcub_cer_5837"
}

Jevtić, I., Penjišević, J.,& Kostić-Rajačić, S.. (2021). Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors. in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event
The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society., 119-119.
https://hdl.handle.net/21.15107/rcub_cer_5837

Jevtić I, Penjišević J, Kostić-Rajačić S. Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors. in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event. 2021;:119-119.
https://hdl.handle.net/21.15107/rcub_cer_5837 .

Jevtić, Ivana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors" in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event (2021):119-119,
https://hdl.handle.net/21.15107/rcub_cer_5837 .

TY  - CONF
AU  - Krunić, Mihajlo
AU  - Penjišević, Jelena
AU  - Jevtić, Ivana
AU  - Ivanović, Milovan
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5843
AB  - Alzheimer’s disease (AD) is a neurodegenerative disease which affects over 50 milion people worldwide.1) AD
mainly affects people ages 65 and above. Symptoms are memory loss, decline in learning capacity, and language
problems. One of currently available treatments for Alzheimer's disease consists of Cholinesterase (ChEIs)
inhibitors, which raise acetylcholine levels in the brain. The drugs currently approved by the FDA for this
purpose are donepezil, rivastigmine and galantamine.
As a part of our research we designed and synthesized seven novel compounds (6a-g) as potential
acetylcholinesterase inhibitors (AChEIs). The compounds contain N-benzyl piperidine moiety, which is common
in many inhibitors including donepezil,2) and N-aryl piperazine moieties.
PB  - Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society
PB  - European Federation  for Medicinal Chemistry and Chemical Biology (EFMC)
C3  - Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event
T1  - Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors
SP  - 413
EP  - 413
UR  - https://hdl.handle.net/21.15107/rcub_cer_5843
ER  - 

@conference{
author = "Krunić, Mihajlo and Penjišević, Jelena and Jevtić, Ivana and Ivanović, Milovan and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "Alzheimer’s disease (AD) is a neurodegenerative disease which affects over 50 milion people worldwide.1) AD
mainly affects people ages 65 and above. Symptoms are memory loss, decline in learning capacity, and language
problems. One of currently available treatments for Alzheimer's disease consists of Cholinesterase (ChEIs)
inhibitors, which raise acetylcholine levels in the brain. The drugs currently approved by the FDA for this
purpose are donepezil, rivastigmine and galantamine.
As a part of our research we designed and synthesized seven novel compounds (6a-g) as potential
acetylcholinesterase inhibitors (AChEIs). The compounds contain N-benzyl piperidine moiety, which is common
in many inhibitors including donepezil,2) and N-aryl piperazine moieties.",
publisher = "Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society, European Federation  for Medicinal Chemistry and Chemical Biology (EFMC)",
journal = "Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event",
title = "Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors",
pages = "413-413",
url = "https://hdl.handle.net/21.15107/rcub_cer_5843"
}

Krunić, M., Penjišević, J., Jevtić, I., Ivanović, M.,& Kostić-Rajačić, S.. (2021). Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors. in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event
Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society., 413-413.
https://hdl.handle.net/21.15107/rcub_cer_5843

Krunić M, Penjišević J, Jevtić I, Ivanović M, Kostić-Rajačić S. Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors. in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event. 2021;:413-413.
https://hdl.handle.net/21.15107/rcub_cer_5843 .

Krunić, Mihajlo, Penjišević, Jelena, Jevtić, Ivana, Ivanović, Milovan, Kostić-Rajačić, Slađana, "Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors" in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event (2021):413-413,
https://hdl.handle.net/21.15107/rcub_cer_5843 .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Savić-Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3999
AB  - Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores, respectively. The synthesis encompassed four steps, securing the final products in 28–42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radioligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, the compounds of the general structure prepared in this research are unlikely to be useful as opioid–dopamine receptor heterobivalent ligands.
AB  - У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation
T1  - Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje
VL  - 85
IS  - 6
SP  - 711
EP  - 720
DO  - 10.2298/JSC190912118J
ER  - 

@article{
author = "Jevtić, Ivana and Penjišević, Jelena and Savić-Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan and Kostić Rajačić, Slađana",
year = "2020",
abstract = "Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores, respectively. The synthesis encompassed four steps, securing the final products in 28–42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radioligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, the compounds of the general structure prepared in this research are unlikely to be useful as opioid–dopamine receptor heterobivalent ligands., У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation, Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje",
volume = "85",
number = "6",
pages = "711-720",
doi = "10.2298/JSC190912118J"
}

Jevtić, I., Penjišević, J., Savić-Vujović, K., Srebro, D., Vučković, S., Ivanović, M.,& Kostić Rajačić, S.. (2020). μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 85(6), 711-720.
https://doi.org/10.2298/JSC190912118J

Jevtić I, Penjišević J, Savić-Vujović K, Srebro D, Vučković S, Ivanović M, Kostić Rajačić S. μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society. 2020;85(6):711-720.
doi:10.2298/JSC190912118J .

Jevtić, Ivana, Penjišević, Jelena, Savić-Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan, Kostić Rajačić, Slađana, "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation" in Journal of the Serbian Chemical Society, 85, no. 6 (2020):711-720,
https://doi.org/10.2298/JSC190912118J . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Lai, Thu Hang
AU  - Penjišević, Jelena
AU  - Dukić-Stefanović, Sladjana
AU  - Andrić, Deana
AU  - Brust, Peter
AU  - Kostić Rajačić, Slađana
AU  - Teodoro, Rodrigo
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4040
AB  - Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.
PB  - MDPI
T2  - Molecules
T1  - Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
VL  - 25
IS  - 21
SP  - 4941
DO  - 10.3390/molecules25214941
ER  - 

@article{
author = "Jevtić, Ivana and Lai, Thu Hang and Penjišević, Jelena and Dukić-Stefanović, Sladjana and Andrić, Deana and Brust, Peter and Kostić Rajačić, Slađana and Teodoro, Rodrigo",
year = "2020",
abstract = "Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.",
publisher = "MDPI",
journal = "Molecules",
title = "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding",
volume = "25",
number = "21",
pages = "4941",
doi = "10.3390/molecules25214941"
}

Jevtić, I., Lai, T. H., Penjišević, J., Dukić-Stefanović, S., Andrić, D., Brust, P., Kostić Rajačić, S.,& Teodoro, R.. (2020). Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules
MDPI., 25(21), 4941.
https://doi.org/10.3390/molecules25214941

Jevtić I, Lai TH, Penjišević J, Dukić-Stefanović S, Andrić D, Brust P, Kostić Rajačić S, Teodoro R. Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules. 2020;25(21):4941.
doi:10.3390/molecules25214941 .

Jevtić, Ivana, Lai, Thu Hang, Penjišević, Jelena, Dukić-Stefanović, Sladjana, Andrić, Deana, Brust, Peter, Kostić Rajačić, Slađana, Teodoro, Rodrigo, "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding" in Molecules, 25, no. 21 (2020):4941,
https://doi.org/10.3390/molecules25214941 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Lai, Hang
AU  - Penjišević, Jelena
AU  - Teodoro, Rodrigo
AU  - Dukic-Stefanovic, Sladjana
AU  - Brust, Peter
AU  - Kostić-Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5836
AB  - The aim of this study was to develop highly specific radiofluorinated ligands for quantitative positron emission tomography (PET) imaging of monoamine oxidase-B (MAO-B) in brain. A series of 8 fluoro derivatives of 1-cinnamyl-4-arylpiperazine were synthesized by standard methods of organic synthesis. The affinity of the compounds was determined in a competitive binding assay using L-[3H] deprenyl as radioligand on rat brain homogenates. The KD of the radioligand was determined by homologous competition. An efficient, three-step procedure for the synthesis of the potential MAO-B ligands was developed. A competitive binding assay was established, using L-[3H]deprenyl as the radioligand, and rat brain membrane homogenate. The compounds were screened (three concentrations 10-9, 10-7 and 10-5) for their MAO-B affinity. We successfully synthesized a series of fluorinated MAO-B ligands. Unfortunately, their affinities toward MAO-B have proved to be rather low. To increase the affinity further modifications are needed.
PB  - Serbian Neuroscience Society / Društvo za neuronauke Srbije
PB  - National Neurocience Society of Romania
PB  - Neuroscience Society of Turkey
C3  - Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia
T1  - Synthesis and biological evaluation of new, potential MAO-B ligands.
SP  - 286
EP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_cer_5836
ER  - 

@conference{
author = "Jevtić, Ivana and Lai, Hang and Penjišević, Jelena and Teodoro, Rodrigo and Dukic-Stefanovic, Sladjana and Brust, Peter and Kostić-Rajačić, Slađana",
year = "2019",
abstract = "The aim of this study was to develop highly specific radiofluorinated ligands for quantitative positron emission tomography (PET) imaging of monoamine oxidase-B (MAO-B) in brain. A series of 8 fluoro derivatives of 1-cinnamyl-4-arylpiperazine were synthesized by standard methods of organic synthesis. The affinity of the compounds was determined in a competitive binding assay using L-[3H] deprenyl as radioligand on rat brain homogenates. The KD of the radioligand was determined by homologous competition. An efficient, three-step procedure for the synthesis of the potential MAO-B ligands was developed. A competitive binding assay was established, using L-[3H]deprenyl as the radioligand, and rat brain membrane homogenate. The compounds were screened (three concentrations 10-9, 10-7 and 10-5) for their MAO-B affinity. We successfully synthesized a series of fluorinated MAO-B ligands. Unfortunately, their affinities toward MAO-B have proved to be rather low. To increase the affinity further modifications are needed.",
publisher = "Serbian Neuroscience Society / Društvo za neuronauke Srbije, National Neurocience Society of Romania, Neuroscience Society of Turkey",
journal = "Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia",
title = "Synthesis and biological evaluation of new, potential MAO-B ligands.",
pages = "286-286",
url = "https://hdl.handle.net/21.15107/rcub_cer_5836"
}

Jevtić, I., Lai, H., Penjišević, J., Teodoro, R., Dukic-Stefanovic, S., Brust, P.,& Kostić-Rajačić, S.. (2019). Synthesis and biological evaluation of new, potential MAO-B ligands.. in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia
Serbian Neuroscience Society / Društvo za neuronauke Srbije., 286-286.
https://hdl.handle.net/21.15107/rcub_cer_5836

Jevtić I, Lai H, Penjišević J, Teodoro R, Dukic-Stefanovic S, Brust P, Kostić-Rajačić S. Synthesis and biological evaluation of new, potential MAO-B ligands.. in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia. 2019;:286-286.
https://hdl.handle.net/21.15107/rcub_cer_5836 .

Jevtić, Ivana, Lai, Hang, Penjišević, Jelena, Teodoro, Rodrigo, Dukic-Stefanovic, Sladjana, Brust, Peter, Kostić-Rajačić, Slađana, "Synthesis and biological evaluation of new, potential MAO-B ligands." in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia (2019):286-286,
https://hdl.handle.net/21.15107/rcub_cer_5836 .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3249
AB  - A scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds that contain both opioid and dopamine pharmacophores linked by the four methylene group chain were synthesized in 33, 35 and 39 % overall yield after a four-step synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4- piperidone. The synthesis presented in this paper could be of interest for heterocyclic and general organic chemistry. The newly designed compounds possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for the further understanding of tolerance and dependence phenomena in opioid clinical use and/or abuse.
AB  - Три нова једињења, која садрже опиоидну и допаминску фармакофору, спојене преко четири метиленске групе, синтетисанa су у четири фазе у укупном приносу од приближно 35 %, полазећи од три комерцијално доступна N-арилпиперазина. Анилино- пиперидински прекурсор је добијен у три једноставне реакционе фазе, полазећи од 4-пиперидона, према познатој литературној методи. Синтеза приказана у овом раду може бити од значаја за хетероцикличну и органску хемију у целини. Новосинтетисана једињења која поседују две фармакофоре, опиоидну и Д2/Д3, су потенцијално корисни супстрати за фармаколошка испитивања. Од посебног интереса може бити истовремено везивање за опиоидне и Д2/Д3 рецепторе, а резултујући фармаколошки одговор био би користан у даљем разумевању толеранције и зависности, као феномена везаних за кли- ничку употребу и/или злоупотребу опијата.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores
T1  - Синтетички пут за синтезу потенцијалних, бивалентних лиганада који поседују опоидну и допамин Д2/Д3 фармакогфору
VL  - 84
IS  - 7
SP  - 639
EP  - 647
DO  - 10.2298/JSC181002105J
ER  - 

@article{
author = "Jevtić, Ivana and Penjišević, Jelena and Ivanović, Milovan D. and Kostić Rajačić, Slađana",
year = "2019",
abstract = "A scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds that contain both opioid and dopamine pharmacophores linked by the four methylene group chain were synthesized in 33, 35 and 39 % overall yield after a four-step synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4- piperidone. The synthesis presented in this paper could be of interest for heterocyclic and general organic chemistry. The newly designed compounds possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for the further understanding of tolerance and dependence phenomena in opioid clinical use and/or abuse., Три нова једињења, која садрже опиоидну и допаминску фармакофору, спојене преко четири метиленске групе, синтетисанa су у четири фазе у укупном приносу од приближно 35 %, полазећи од три комерцијално доступна N-арилпиперазина. Анилино- пиперидински прекурсор је добијен у три једноставне реакционе фазе, полазећи од 4-пиперидона, према познатој литературној методи. Синтеза приказана у овом раду може бити од значаја за хетероцикличну и органску хемију у целини. Новосинтетисана једињења која поседују две фармакофоре, опиоидну и Д2/Д3, су потенцијално корисни супстрати за фармаколошка испитивања. Од посебног интереса може бити истовремено везивање за опиоидне и Д2/Д3 рецепторе, а резултујући фармаколошки одговор био би користан у даљем разумевању толеранције и зависности, као феномена везаних за кли- ничку употребу и/или злоупотребу опијата.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores, Синтетички пут за синтезу потенцијалних, бивалентних лиганада који поседују опоидну и допамин Д2/Д3 фармакогфору",
volume = "84",
number = "7",
pages = "639-647",
doi = "10.2298/JSC181002105J"
}

Jevtić, I., Penjišević, J., Ivanović, M. D.,& Kostić Rajačić, S.. (2019). Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 84(7), 639-647.
https://doi.org/10.2298/JSC181002105J

Jevtić I, Penjišević J, Ivanović MD, Kostić Rajačić S. Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores. in Journal of the Serbian Chemical Society. 2019;84(7):639-647.
doi:10.2298/JSC181002105J .

Jevtić, Ivana, Penjišević, Jelena, Ivanović, Milovan D., Kostić Rajačić, Slađana, "Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores" in Journal of the Serbian Chemical Society, 84, no. 7 (2019):639-647,
https://doi.org/10.2298/JSC181002105J . .

TY  - CONF
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Dukic-Stefanovic, Sladjana
AU  - Spalholz, Tina
AU  - Burst, Peter
AU  - Kostić-Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5833
AB  - Serotonin 5HT1a receptor belongs to a class of G-protein coupled receptors. It serves as a
potential target for neurological disorders such as depression, anxiety etc. It is a well-known
fact that N-arylpiperazine moiety is present in compounds with pronounced 5HT1a activity.
Taking into account previously published results1 novel structures of N-{4-[2-(4-
arylpiperazin-1-yl)ethyl]phenyl}arylamides (Figure 1.) were designed for target synthesis.
Proposed modifications include: different position of hydroxyl group in aryl amide part of
molecule and addition of methoxy and chloro substituents to the phenyl ring of parent
compounds, since their introduction in the molecule leads to increased receptor affinity.
New compounds were synthesized by acylation of N-arylpiperazines using 4-
nitrophenylacetic acid. Obtained amides were converted in 1-(4-nitrophenethyl)-4-
arylpiperazines using diborane in THF. Reduction of nitro compounds by Ra/Ni provided 1-
(4-aminophenethyl)-4-arylpiperazines. Target arylamides were obtained by condensation 1-
(4-aminophenethyl)-4-arylpiperazines with corresponding aryl acids in presence of
propylphosphoric acid anhydride (PPAA) in DMF.
All newly synthesized compounds were evaluated for their activity toward 5HT1a receptors
by in vitro competitive displacement assay of [3H] 8-OH-DPAT. HEK cell line were used as a
source of 5HT1a receptors.
Introduction of 2-methoxy and 2,3-dichloro groups,as well as meta and para hydroxyl group
in molecule resulted in increment of affinity toward 5HT1a receptors comparing to the parent
compounds.
PB  - European federation for medicinal chemistry (EFMC)
C3  - 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic
T1  - Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides
SP  - P-64
UR  - https://hdl.handle.net/21.15107/rcub_cer_5833
ER  - 

@conference{
author = "Penjišević, Jelena and Andrić, Deana and Dukic-Stefanovic, Sladjana and Spalholz, Tina and Burst, Peter and Kostić-Rajačić, Slađana",
year = "2019",
abstract = "Serotonin 5HT1a receptor belongs to a class of G-protein coupled receptors. It serves as a
potential target for neurological disorders such as depression, anxiety etc. It is a well-known
fact that N-arylpiperazine moiety is present in compounds with pronounced 5HT1a activity.
Taking into account previously published results1 novel structures of N-{4-[2-(4-
arylpiperazin-1-yl)ethyl]phenyl}arylamides (Figure 1.) were designed for target synthesis.
Proposed modifications include: different position of hydroxyl group in aryl amide part of
molecule and addition of methoxy and chloro substituents to the phenyl ring of parent
compounds, since their introduction in the molecule leads to increased receptor affinity.
New compounds were synthesized by acylation of N-arylpiperazines using 4-
nitrophenylacetic acid. Obtained amides were converted in 1-(4-nitrophenethyl)-4-
arylpiperazines using diborane in THF. Reduction of nitro compounds by Ra/Ni provided 1-
(4-aminophenethyl)-4-arylpiperazines. Target arylamides were obtained by condensation 1-
(4-aminophenethyl)-4-arylpiperazines with corresponding aryl acids in presence of
propylphosphoric acid anhydride (PPAA) in DMF.
All newly synthesized compounds were evaluated for their activity toward 5HT1a receptors
by in vitro competitive displacement assay of [3H] 8-OH-DPAT. HEK cell line were used as a
source of 5HT1a receptors.
Introduction of 2-methoxy and 2,3-dichloro groups,as well as meta and para hydroxyl group
in molecule resulted in increment of affinity toward 5HT1a receptors comparing to the parent
compounds.",
publisher = "European federation for medicinal chemistry (EFMC)",
journal = "11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic",
title = "Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides",
pages = "P-64",
url = "https://hdl.handle.net/21.15107/rcub_cer_5833"
}

Penjišević, J., Andrić, D., Dukic-Stefanovic, S., Spalholz, T., Burst, P.,& Kostić-Rajačić, S.. (2019). Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides. in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic
European federation for medicinal chemistry (EFMC)., P-64.
https://hdl.handle.net/21.15107/rcub_cer_5833

Penjišević J, Andrić D, Dukic-Stefanovic S, Spalholz T, Burst P, Kostić-Rajačić S. Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides. in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic. 2019;:P-64.
https://hdl.handle.net/21.15107/rcub_cer_5833 .

Penjišević, Jelena, Andrić, Deana, Dukic-Stefanovic, Sladjana, Spalholz, Tina, Burst, Peter, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of N-{4-[2-(4-arylpiperazin-1-      yl)ethyl]phenyl} arylamides" in 11th Joint Meeting on Medicinal Chemistry, Final Programme, Јune 27-30, 2019,  Prague, Czech Republic (2019):P-64,
https://hdl.handle.net/21.15107/rcub_cer_5833 .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Šukalović, Vladimir
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2654
AB  - A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (D2DR) in a [3H]spiperone competition assay. All herein described compounds consist of a benzimidazole moiety connected to the N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on D2DR-arylpiperazine complexes with an
objective to explore the receptor-ligand interactions and properties of the receptor binding site. Crystal structure of D2DR that has been published recently was used throughout this study.
The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of D2DR and thereforeshould contain a linker of 5 or 6 methylene groups long.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor
VL  - 84
IS  - 9
SP  - 925
EP  - 934
DO  - 10.2298/JSC181029104P
ER  - 

@article{
author = "Penjišević, Jelena and Andrić, Deana and Šukalović, Vladimir and Roglić, Goran and Šoškić, Vukić and Kostić Rajačić, Slađana",
year = "2019",
abstract = "A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (D2DR) in a [3H]spiperone competition assay. All herein described compounds consist of a benzimidazole moiety connected to the N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on D2DR-arylpiperazine complexes with an
objective to explore the receptor-ligand interactions and properties of the receptor binding site. Crystal structure of D2DR that has been published recently was used throughout this study.
The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of D2DR and thereforeshould contain a linker of 5 or 6 methylene groups long.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor",
volume = "84",
number = "9",
pages = "925-934",
doi = "10.2298/JSC181029104P"
}

Penjišević, J., Andrić, D., Šukalović, V., Roglić, G., Šoškić, V.,& Kostić Rajačić, S.. (2019). Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 84(9), 925-934.
https://doi.org/10.2298/JSC181029104P

Penjišević J, Andrić D, Šukalović V, Roglić G, Šoškić V, Kostić Rajačić S. Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society. 2019;84(9):925-934.
doi:10.2298/JSC181029104P .

Penjišević, Jelena, Andrić, Deana, Šukalović, Vladimir, Roglić, Goran, Šoškić, Vukić, Kostić Rajačić, Slađana, "Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor" in Journal of the Serbian Chemical Society, 84, no. 9 (2019):925-934,
https://doi.org/10.2298/JSC181029104P . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Milojković-Opsenica, Dušanka
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2991
AB  - Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values
determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.
PB  - Elsevier
T2  - Journal of Chromatography B
T1  - Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands
VL  - 1124
SP  - 146
EP  - 153
DO  - 10.1016/j.jchromb.2019.06.006
ER  - 

@article{
author = "Šegan, Sandra and Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Milojković-Opsenica, Dušanka and Kostić Rajačić, Slađana",
year = "2019",
abstract = "Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values
determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.",
publisher = "Elsevier",
journal = "Journal of Chromatography B",
title = "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands",
volume = "1124",
pages = "146-153",
doi = "10.1016/j.jchromb.2019.06.006"
}

Šegan, S., Penjišević, J., Šukalović, V., Andrić, D., Milojković-Opsenica, D.,& Kostić Rajačić, S.. (2019). Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B
Elsevier., 1124, 146-153.
https://doi.org/10.1016/j.jchromb.2019.06.006

Šegan S, Penjišević J, Šukalović V, Andrić D, Milojković-Opsenica D, Kostić Rajačić S. Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B. 2019;1124:146-153.
doi:10.1016/j.jchromb.2019.06.006 .

Šegan, Sandra, Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Milojković-Opsenica, Dušanka, Kostić Rajačić, Slađana, "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands" in Journal of Chromatography B, 1124 (2019):146-153,
https://doi.org/10.1016/j.jchromb.2019.06.006 . .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Šukalović, Vladimir
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3097
AB  - A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (D2DR) in a [3H]spiperone competition assay. All herein described compounds consist of a benzimidazole moiety connected to the N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on D2DR-arylpiperazine complexes with anobjective to explore the receptor-ligand interactions and properties of the receptor binding site. Crystal structure of D2DR that has been published recently was used throughout this study.The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of D2DR and thereforeshould contain a linker of 5 or 6 methylene groups long.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor
VL  - 84
IS  - 9
SP  - 925
EP  - 934
DO  - 10.2298/JSC181029104P
ER  - 

@article{
author = "Penjišević, Jelena and Andrić, Deana and Šukalović, Vladimir and Roglić, Goran and Šoškić, Vukić and Kostić Rajačić, Slađana",
year = "2019",
abstract = "A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (D2DR) in a [3H]spiperone competition assay. All herein described compounds consist of a benzimidazole moiety connected to the N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on D2DR-arylpiperazine complexes with anobjective to explore the receptor-ligand interactions and properties of the receptor binding site. Crystal structure of D2DR that has been published recently was used throughout this study.The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of D2DR and thereforeshould contain a linker of 5 or 6 methylene groups long.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor",
volume = "84",
number = "9",
pages = "925-934",
doi = "10.2298/JSC181029104P"
}

Penjišević, J., Andrić, D., Šukalović, V., Roglić, G., Šoškić, V.,& Kostić Rajačić, S.. (2019). Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 84(9), 925-934.
https://doi.org/10.2298/JSC181029104P

Penjišević J, Andrić D, Šukalović V, Roglić G, Šoškić V, Kostić Rajačić S. Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society. 2019;84(9):925-934.
doi:10.2298/JSC181029104P .

Penjišević, Jelena, Andrić, Deana, Šukalović, Vladimir, Roglić, Goran, Šoškić, Vukić, Kostić Rajačić, Slađana, "Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor" in Journal of the Serbian Chemical Society, 84, no. 9 (2019):925-934,
https://doi.org/10.2298/JSC181029104P . .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Andrić, Deana B.
AU  - Šukalović, Vladimir
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3316
AB  - A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (DRD2) in a [3H]spiperone competition assay. All the herein described compounds consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on the DRD2–arylpiperazine complexes with the objective of exploring the receptor–ligand interactions and properties of the receptor binding site. The recently published crystal structure of DRD2 was used throughout this study. The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of DRD2 and therefore should contain a linker of 5 or 6 methylene groups long
AB  - У овом раду је презентована синтеза 14 нових арилпиперазина и одређен је њихов
афинитет везивања за Д2 допамински рецептор (DRD2) тестовима компетиције са
[3H]спипероном. По својој хемијској структури ова једињења представљају супституисане
бензимидазоле повезане са N-(2-метоксифенил)пиперазинским делом, линкерима разли-
читих дужина. У циљу испитивања лиганд-рецептор интеракција и особина везивног места
DRD2, урађена је докинг анализа новосинтетисаних једињења и симулација молекулске
динамике, користећи кристалну структуру рецептора. Резултати добијени у овом раду
указују да арилпиперазини високог афинитета остварују интеракције у ортостерном везивном месту и у екстензији ортостерног места везивања DRD2 и да стога треба да поседују
линкер оптималне дужине, од 5 или 6 метиленских група.
PB  - Beograd : Srpsko hemijsko društvo
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor
VL  - 84
IS  - 9
SP  - 925
EP  - 934
DO  - 10.2298/JSC181029104P
ER  - 

@article{
author = "Penjišević, Jelena and Andrić, Deana B. and Šukalović, Vladimir and Roglić, Goran and Šoškić, Vukić and Kostić Rajačić, Slađana",
year = "2019",
abstract = "A total of 14 novel arylpiperazines were synthesized, and pharmacologically evaluated by measuring their affinities towards the D2 dopamine receptor (DRD2) in a [3H]spiperone competition assay. All the herein described compounds consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on the DRD2–arylpiperazine complexes with the objective of exploring the receptor–ligand interactions and properties of the receptor binding site. The recently published crystal structure of DRD2 was used throughout this study. The major finding is that high affinity arylpiperazines must interact with both the orthosteric binding site and the extended binding pocket of DRD2 and therefore should contain a linker of 5 or 6 methylene groups long, У овом раду је презентована синтеза 14 нових арилпиперазина и одређен је њихов
афинитет везивања за Д2 допамински рецептор (DRD2) тестовима компетиције са
[3H]спипероном. По својој хемијској структури ова једињења представљају супституисане
бензимидазоле повезане са N-(2-метоксифенил)пиперазинским делом, линкерима разли-
читих дужина. У циљу испитивања лиганд-рецептор интеракција и особина везивног места
DRD2, урађена је докинг анализа новосинтетисаних једињења и симулација молекулске
динамике, користећи кристалну структуру рецептора. Резултати добијени у овом раду
указују да арилпиперазини високог афинитета остварују интеракције у ортостерном везивном месту и у екстензији ортостерног места везивања DRD2 и да стога треба да поседују
линкер оптималне дужине, од 5 или 6 метиленских група.",
publisher = "Beograd : Srpsko hemijsko društvo",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor",
volume = "84",
number = "9",
pages = "925-934",
doi = "10.2298/JSC181029104P"
}

Penjišević, J., Andrić, D. B., Šukalović, V., Roglić, G., Šoškić, V.,& Kostić Rajačić, S.. (2019). Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society
Beograd : Srpsko hemijsko društvo., 84(9), 925-934.
https://doi.org/10.2298/JSC181029104P

Penjišević J, Andrić DB, Šukalović V, Roglić G, Šoškić V, Kostić Rajačić S. Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor. in Journal of the Serbian Chemical Society. 2019;84(9):925-934.
doi:10.2298/JSC181029104P .

Penjišević, Jelena, Andrić, Deana B., Šukalović, Vladimir, Roglić, Goran, Šoškić, Vukić, Kostić Rajačić, Slađana, "Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor" in Journal of the Serbian Chemical Society, 84, no. 9 (2019):925-934,
https://doi.org/10.2298/JSC181029104P . .

TY  - JOUR
AU  - Kostić Rajačić, Slađana
AU  - Schwall, Gerhard
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2375
AB  - Affinity chromatography was used to identify potential cellular targets that are responsible for neuroprotective activity of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. Active and inactive representatives of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides bearing an extended linker were synthesized and immobilized on an agarose-based matrix. This was followed by the identification of specifically bound proteins isolated out of the whole rat brain extract. Inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) was identified as candidates for cellular targets.
PB  - Wiley, Hoboken
T2  - Chemical Biology & Drug Design
T1  - Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
VL  - 92
IS  - 1
SP  - 1393
EP  - 1397
DO  - 10.1111/cbdd.13193
ER  - 

@article{
author = "Kostić Rajačić, Slađana and Schwall, Gerhard and Penjišević, Jelena and Andrić, Deana and Šukalović, Vladimir and Šoškić, Vukić",
year = "2018",
abstract = "Affinity chromatography was used to identify potential cellular targets that are responsible for neuroprotective activity of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. Active and inactive representatives of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides bearing an extended linker were synthesized and immobilized on an agarose-based matrix. This was followed by the identification of specifically bound proteins isolated out of the whole rat brain extract. Inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) was identified as candidates for cellular targets.",
publisher = "Wiley, Hoboken",
journal = "Chemical Biology & Drug Design",
title = "Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides",
volume = "92",
number = "1",
pages = "1393-1397",
doi = "10.1111/cbdd.13193"
}

Kostić Rajačić, S., Schwall, G., Penjišević, J., Andrić, D., Šukalović, V.,& Šoškić, V.. (2018). Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Chemical Biology & Drug Design
Wiley, Hoboken., 92(1), 1393-1397.
https://doi.org/10.1111/cbdd.13193

Kostić Rajačić S, Schwall G, Penjišević J, Andrić D, Šukalović V, Šoškić V. Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Chemical Biology & Drug Design. 2018;92(1):1393-1397.
doi:10.1111/cbdd.13193 .

Kostić Rajačić, Slađana, Schwall, Gerhard, Penjišević, Jelena, Andrić, Deana, Šukalović, Vladimir, Šoškić, Vukić, "Identification of NQO1 and ferrochelatase as interaction partners for neuroprotective N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in Chemical Biology & Drug Design, 92, no. 1 (2018):1393-1397,
https://doi.org/10.1111/cbdd.13193 . .

TY  - THES
AU  - Penjišević, Jelena
PY  - 2016
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=4906
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:15361/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48823823
UR  - http://nardus.mpn.gov.rs/123456789/8026
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2570
AB  - Poslednjih godina sve više ljudi oboleva od šizofrenije, depresije i drugihneuroloških poremećaja. Njihi izazivaju promene na nivou dopaminergičkog iserotonergičkog sistema u mozgu. Dizajn i sinteza dopaminergičkih i serotonergičkih liganada koji bi našli primenu u lečenju bolesti izazvanih disfunkcijom ovih receptorskih sistema u CNS, a čije korišćenje ne bi izazivalo negativne efekte je primaran zadatak naučnika u oblasti medicinske hemije. Poznavanje strukture receptora, odnosno mesta vezivanja liganada u receptoru, doprinelo bi bržem razvoju potencijalnih lekova. U okviru ove doktorske disertacije uspešno je sintetisano i okarakterisano 46 novih liganada. Ligandi su razvrstani u dve serije: ligandi sa piperidinskim prstenom u mostu između glave (benzil, benzoil, fenetil, fenacetil grupe sa odgovarajućim supstituentima) i repa (2-metoksifenilpiperazin) i ligandi sa različitom dužinom alkil mosta između glave (supstituisani benzimidazoli) i repa (2-metoksifenilpiperazin). Za sve novosintetisane ligande određen je farmakološki profil vezivanja za dopaminske D2, serotoninske 5HT2a i adrenergičke α1 receptore u testovima kompetitivnog vezivanja sa radioaktivno obeleženim ligandima.U seriji liganada sa piperidinskim prstenom u mostu između glave (benzil, benzoil, fenetil, fenacetil grupe sa odgovarajućim supstituentima) i repa (2-metoksifenilpiperazin) uočeno je da supstituisani ligandi pokazuju veći afinitetprema dopaminskim D2 receptorima nego nesupstituisani ligandi. Pored toga, ligandi sa većim stepenom fleksibilnosti (metilenski most između piperidinskog i piperazinskog prstena) pokazali su veći afinitet od rigidnih liganada (piperazinski prsten je direktno vezan za piperidinski prsten). Ova serija liganada pokazala je odsustvo ili slab afinitet prema serotoninskim 5HT2a receptorima.U seriji liganada sa različitom dužinom alkil mosta između benzimidazolskog dela i 2-metoksifenilpiperazina utvrđeno je da najveći afinitet prema dopaminskim D2 redceptorima pokazuju ligandi sa pet i šest ugljenikovih atoma u mostu. Izuzev dvaliganda, ostala jedinjenja iz ove serije poseduju umeren afinitet vezivanja zaserotoninske 5HT2a receptore.U radu je putem doking analize, pored ortosternog mesta vezivanja ispitano i mesto vezivanja dopaminskog D2 receptora koje čini druga ekstracelularna petlja (ecl2).Doking analiza predviđa da ligandi pored toga što ostvaruju aromatične interakcije sa aminokiselinskim ostacima u hidrofobnom džepu receptora Phe 386 (6.44), Trp 390(6.48), Tyr 420 (7.43), formiraju i hidrofobne interakcije sa aminokiselinskim ostacima Phe 393 i His 397 koji se nalaze u ecl2. Takođe, preliminarna doking analiza liganada sa različitom dužinom alkil mosta između glave (supstituisani benzimidazoli) i repa (2-metoksifenilpiperazin), ukazuje na postojanje hidrofobnih interakcija između liganda i Ile 166, Leu 170, Ile 184, Phe 189, Val 111, Ile 398, His 397 iz regiona druge ekstracelularne petlje.
AB  - Schizophrenia, depression and related neurological disorders are modern daydiseases, caused by dopaminergic and serotonergic imbalances in the brain. Design and synthesis of dopaminergic and serotonergic ligands without side effects, which could find application in the treatment of these CNS disorders, is one of the main objectives of medicinal chemistry. Improved understanding of dopamine D2 receptor binding site would contribute to faster development of potential drugs. As a part of this thesis, 46 new ligands were synthesized and characterized. The ligands were grouped into two sets: ligands with a piperidine ring in the bridge between the head (benzyl, benzoyl, phenethyl, and phenylacetyl groups with different substituents) and the tail (2-methoxyphenylpiperazine) and ligands with different lengths of the alkyl bridge between the head (substituted benzimidazoles) and the tail (2-methoxyphenylpiperazine). All newly synthesized ligands were evaluated for D2, 5HT2a and α1 affinity in an in vitro competitive displacement assay using radiolabeled ligands.Among ligands with the piperidine ring in the bridge between the head (benzyl,benzoyl, phenethyl, phenylacetyl groups with different substituents) and the tail(2-methoxyphenylpiperazine), substituted ligands exhibited a higher affinity fordopamine D2 receptors. In addition, ligands with a greater degree of flexibility (a methylene bridge between the piperidine and piperazine rings) demonstrated a higher affinity compared to rigid ligands (the piperazine ring is bound directly to the piperidine ring). This series of ligands displayed no or low affinity for the serotonin 5HT2a receptors.Among ligands with different lengths of the alkyl bridge between the benzimidazole and 2-methoxyphenylpiperazine part of the molecule, highest affinity for the dopamine D2 receptor was demonstrated by ligands with five or six carbon atoms inthe bridge. Compounds in this series, with the exception of two ligands, had a moderate binding affinity for the serotonin 5HT2a receptors.The docking analysis was used to examine the D2 orthosteric binding site andthe alternative binding site formed by the second extracellular loop (ecl2).Preliminary docking analysis predicts that ligands, in addition to the interactions with Phe 386 (6.44), Trp 390 (6.48) and Tyr 420 (7.43) in the hydrophobic pocket of the orthosteric binding site, form hydrophobic interactions with Phe 393 and His 397, located in the ecl2. Likewise, the preliminary docking analysis of ligands with the different lengths of the alkyl bridge between the head (substituted benzimidazoles) and the tail (2-methoxyphenyl piperazine), indicated the existence of hydrophobic interactions between the ligands and Ile 166, Leu 170, Ile 184, Phe 189, Val 111, Ile 398 and His 397, located in the second extracellular loop (ecl2).
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Proučavanje mesta vezivanja dopaminskog D2 receptora novosintetisanim ligandima 2-metoksifenilpiperazinskog tipa
UR  - https://hdl.handle.net/21.15107/rcub_nardus_8026
ER  - 

@phdthesis{
author = "Penjišević, Jelena",
year = "2016",
abstract = "Poslednjih godina sve više ljudi oboleva od šizofrenije, depresije i drugihneuroloških poremećaja. Njihi izazivaju promene na nivou dopaminergičkog iserotonergičkog sistema u mozgu. Dizajn i sinteza dopaminergičkih i serotonergičkih liganada koji bi našli primenu u lečenju bolesti izazvanih disfunkcijom ovih receptorskih sistema u CNS, a čije korišćenje ne bi izazivalo negativne efekte je primaran zadatak naučnika u oblasti medicinske hemije. Poznavanje strukture receptora, odnosno mesta vezivanja liganada u receptoru, doprinelo bi bržem razvoju potencijalnih lekova. U okviru ove doktorske disertacije uspešno je sintetisano i okarakterisano 46 novih liganada. Ligandi su razvrstani u dve serije: ligandi sa piperidinskim prstenom u mostu između glave (benzil, benzoil, fenetil, fenacetil grupe sa odgovarajućim supstituentima) i repa (2-metoksifenilpiperazin) i ligandi sa različitom dužinom alkil mosta između glave (supstituisani benzimidazoli) i repa (2-metoksifenilpiperazin). Za sve novosintetisane ligande određen je farmakološki profil vezivanja za dopaminske D2, serotoninske 5HT2a i adrenergičke α1 receptore u testovima kompetitivnog vezivanja sa radioaktivno obeleženim ligandima.U seriji liganada sa piperidinskim prstenom u mostu između glave (benzil, benzoil, fenetil, fenacetil grupe sa odgovarajućim supstituentima) i repa (2-metoksifenilpiperazin) uočeno je da supstituisani ligandi pokazuju veći afinitetprema dopaminskim D2 receptorima nego nesupstituisani ligandi. Pored toga, ligandi sa većim stepenom fleksibilnosti (metilenski most između piperidinskog i piperazinskog prstena) pokazali su veći afinitet od rigidnih liganada (piperazinski prsten je direktno vezan za piperidinski prsten). Ova serija liganada pokazala je odsustvo ili slab afinitet prema serotoninskim 5HT2a receptorima.U seriji liganada sa različitom dužinom alkil mosta između benzimidazolskog dela i 2-metoksifenilpiperazina utvrđeno je da najveći afinitet prema dopaminskim D2 redceptorima pokazuju ligandi sa pet i šest ugljenikovih atoma u mostu. Izuzev dvaliganda, ostala jedinjenja iz ove serije poseduju umeren afinitet vezivanja zaserotoninske 5HT2a receptore.U radu je putem doking analize, pored ortosternog mesta vezivanja ispitano i mesto vezivanja dopaminskog D2 receptora koje čini druga ekstracelularna petlja (ecl2).Doking analiza predviđa da ligandi pored toga što ostvaruju aromatične interakcije sa aminokiselinskim ostacima u hidrofobnom džepu receptora Phe 386 (6.44), Trp 390(6.48), Tyr 420 (7.43), formiraju i hidrofobne interakcije sa aminokiselinskim ostacima Phe 393 i His 397 koji se nalaze u ecl2. Takođe, preliminarna doking analiza liganada sa različitom dužinom alkil mosta između glave (supstituisani benzimidazoli) i repa (2-metoksifenilpiperazin), ukazuje na postojanje hidrofobnih interakcija između liganda i Ile 166, Leu 170, Ile 184, Phe 189, Val 111, Ile 398, His 397 iz regiona druge ekstracelularne petlje., Schizophrenia, depression and related neurological disorders are modern daydiseases, caused by dopaminergic and serotonergic imbalances in the brain. Design and synthesis of dopaminergic and serotonergic ligands without side effects, which could find application in the treatment of these CNS disorders, is one of the main objectives of medicinal chemistry. Improved understanding of dopamine D2 receptor binding site would contribute to faster development of potential drugs. As a part of this thesis, 46 new ligands were synthesized and characterized. The ligands were grouped into two sets: ligands with a piperidine ring in the bridge between the head (benzyl, benzoyl, phenethyl, and phenylacetyl groups with different substituents) and the tail (2-methoxyphenylpiperazine) and ligands with different lengths of the alkyl bridge between the head (substituted benzimidazoles) and the tail (2-methoxyphenylpiperazine). All newly synthesized ligands were evaluated for D2, 5HT2a and α1 affinity in an in vitro competitive displacement assay using radiolabeled ligands.Among ligands with the piperidine ring in the bridge between the head (benzyl,benzoyl, phenethyl, phenylacetyl groups with different substituents) and the tail(2-methoxyphenylpiperazine), substituted ligands exhibited a higher affinity fordopamine D2 receptors. In addition, ligands with a greater degree of flexibility (a methylene bridge between the piperidine and piperazine rings) demonstrated a higher affinity compared to rigid ligands (the piperazine ring is bound directly to the piperidine ring). This series of ligands displayed no or low affinity for the serotonin 5HT2a receptors.Among ligands with different lengths of the alkyl bridge between the benzimidazole and 2-methoxyphenylpiperazine part of the molecule, highest affinity for the dopamine D2 receptor was demonstrated by ligands with five or six carbon atoms inthe bridge. Compounds in this series, with the exception of two ligands, had a moderate binding affinity for the serotonin 5HT2a receptors.The docking analysis was used to examine the D2 orthosteric binding site andthe alternative binding site formed by the second extracellular loop (ecl2).Preliminary docking analysis predicts that ligands, in addition to the interactions with Phe 386 (6.44), Trp 390 (6.48) and Tyr 420 (7.43) in the hydrophobic pocket of the orthosteric binding site, form hydrophobic interactions with Phe 393 and His 397, located in the ecl2. Likewise, the preliminary docking analysis of ligands with the different lengths of the alkyl bridge between the head (substituted benzimidazoles) and the tail (2-methoxyphenyl piperazine), indicated the existence of hydrophobic interactions between the ligands and Ile 166, Leu 170, Ile 184, Phe 189, Val 111, Ile 398 and His 397, located in the second extracellular loop (ecl2).",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Proučavanje mesta vezivanja dopaminskog D2 receptora novosintetisanim ligandima 2-metoksifenilpiperazinskog tipa",
url = "https://hdl.handle.net/21.15107/rcub_nardus_8026"
}

Penjišević, J.. (2016). Proučavanje mesta vezivanja dopaminskog D2 receptora novosintetisanim ligandima 2-metoksifenilpiperazinskog tipa. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_8026

Penjišević J. Proučavanje mesta vezivanja dopaminskog D2 receptora novosintetisanim ligandima 2-metoksifenilpiperazinskog tipa. in Универзитет у Београду. 2016;.
https://hdl.handle.net/21.15107/rcub_nardus_8026 .

Penjišević, Jelena, "Proučavanje mesta vezivanja dopaminskog D2 receptora novosintetisanim ligandima 2-metoksifenilpiperazinskog tipa" in Универзитет у Београду (2016),
https://hdl.handle.net/21.15107/rcub_nardus_8026 .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1880
AB  - Sixteen new 1-(2-methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines were synthesized to be used as probes for mapping the dopamine D-2 receptor (D(2)DAR) arylpiperazine binding site. All compounds were evaluated for their affinity toward D(2)DAR in an in vitro competitive displacement assay. The most active one was 1-(2-methoxyphenyl)-4-{[1-(3-nitrophenethyl)piperidin-4-yl]methyl}piperazine (25) with an affinity of K-i = 54 nM. Docking analysis was conducted on all herein described compounds, whereas molecular dynamic simulation was performed on ligand 25 to establish its mode of interaction with D(2)DAR. Two possible docking orientations are proposed; the one with a salt bridge between the piperidine moiety and Asp114 of D(2)DAR is more stable.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv der Pharmazie
T1  - Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands
VL  - 349
IS  - 8
SP  - 614
EP  - 626
DO  - 10.1002/ardp.201600081
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Roglić, Goran and Šoškić, Vukić and Kostić Rajačić, Slađana",
year = "2016",
abstract = "Sixteen new 1-(2-methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines were synthesized to be used as probes for mapping the dopamine D-2 receptor (D(2)DAR) arylpiperazine binding site. All compounds were evaluated for their affinity toward D(2)DAR in an in vitro competitive displacement assay. The most active one was 1-(2-methoxyphenyl)-4-{[1-(3-nitrophenethyl)piperidin-4-yl]methyl}piperazine (25) with an affinity of K-i = 54 nM. Docking analysis was conducted on all herein described compounds, whereas molecular dynamic simulation was performed on ligand 25 to establish its mode of interaction with D(2)DAR. Two possible docking orientations are proposed; the one with a salt bridge between the piperidine moiety and Asp114 of D(2)DAR is more stable.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv der Pharmazie",
title = "Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands",
volume = "349",
number = "8",
pages = "614-626",
doi = "10.1002/ardp.201600081"
}

Penjišević, J., Šukalović, V., Andrić, D., Roglić, G., Šoškić, V.,& Kostić Rajačić, S.. (2016). Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands. in Archiv der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 349(8), 614-626.
https://doi.org/10.1002/ardp.201600081

Penjišević J, Šukalović V, Andrić D, Roglić G, Šoškić V, Kostić Rajačić S. Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands. in Archiv der Pharmazie. 2016;349(8):614-626.
doi:10.1002/ardp.201600081 .

Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Roglić, Goran, Šoškić, Vukić, Kostić Rajačić, Slađana, "Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands" in Archiv der Pharmazie, 349, no. 8 (2016):614-626,
https://doi.org/10.1002/ardp.201600081 . .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Novaković, Irena
AU  - Šoškić, Vukić
AU  - Kostić Rajačić, Slađana
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2017
AB  - A series of sixteen novel substituted piperidines and (2-methoxyphenyl)piperazines were synthesized, starting from the key intermediates 1-(2-methoxyphenyl)-4-(piperidin-4-yl)piperazine and 1-(2-methoxyphenyl)-4-[(piperidin-4-yl)methyl] piperazine. Biological evaluation of the synthesized compounds was illustrated by seven compounds, of which 1-(2-methoxyphenyl)-4-{[1-(2-nitrobenzyl) piperidin-4-yl] methyl} piperazine had the highest affinity for the dopamine D-2 receptor. For all seven selected compounds, docking analysis was performed in order to establish their structure-to-activity relationship.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis, biological evaluation and docking analysis of substituted piperidines and (2-methoxyphenyl)piperazines
VL  - 81
IS  - 4
SP  - 347
EP  - 356
DO  - 10.2298/JSC151021097P
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Roglić, Goran and Novaković, Irena and Šoškić, Vukić and Kostić Rajačić, Slađana",
year = "2016",
abstract = "A series of sixteen novel substituted piperidines and (2-methoxyphenyl)piperazines were synthesized, starting from the key intermediates 1-(2-methoxyphenyl)-4-(piperidin-4-yl)piperazine and 1-(2-methoxyphenyl)-4-[(piperidin-4-yl)methyl] piperazine. Biological evaluation of the synthesized compounds was illustrated by seven compounds, of which 1-(2-methoxyphenyl)-4-{[1-(2-nitrobenzyl) piperidin-4-yl] methyl} piperazine had the highest affinity for the dopamine D-2 receptor. For all seven selected compounds, docking analysis was performed in order to establish their structure-to-activity relationship.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis, biological evaluation and docking analysis of substituted piperidines and (2-methoxyphenyl)piperazines",
volume = "81",
number = "4",
pages = "347-356",
doi = "10.2298/JSC151021097P"
}

Penjišević, J., Šukalović, V., Andrić, D., Roglić, G., Novaković, I., Šoškić, V.,& Kostić Rajačić, S.. (2016). Synthesis, biological evaluation and docking analysis of substituted piperidines and (2-methoxyphenyl)piperazines. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 81(4), 347-356.
https://doi.org/10.2298/JSC151021097P

Penjišević J, Šukalović V, Andrić D, Roglić G, Novaković I, Šoškić V, Kostić Rajačić S. Synthesis, biological evaluation and docking analysis of substituted piperidines and (2-methoxyphenyl)piperazines. in Journal of the Serbian Chemical Society. 2016;81(4):347-356.
doi:10.2298/JSC151021097P .

Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Roglić, Goran, Novaković, Irena, Šoškić, Vukić, Kostić Rajačić, Slađana, "Synthesis, biological evaluation and docking analysis of substituted piperidines and (2-methoxyphenyl)piperazines" in Journal of the Serbian Chemical Society, 81, no. 4 (2016):347-356,
https://doi.org/10.2298/JSC151021097P . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Ignjatović, Đurđica S.
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić Rajačić, Slađana
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1488
AB  - The dopaminergic receptor system has been the focus for the development of new pharmacotherapeutic agents targeting a number of central nervous system related disorders, such as drug addiction, schizophrenia, depression, and Parkinson's disease, to name just a few. To date, the crystal structure for the human D2 receptor is not known, despite its vital function and importance as a therapeutic target. Herein, a recent advancement in the determination of key receptor ligand interactions for the available arylpiperazine-like ligands, using a D2 receptor model based on the crystal structure of the D3 receptor is presented. To determine key interactions responsible for high dopaminergic activity, computer-docking analysis was used together with experimental data. A total of 4 dopaminergic ligands showing moderate to high affinity were tested and the obtained results rationalized using ligand structures docked into the proposed D2 receptor model.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Investigation of key interactions between the second extracellular loop of the dopamine D2 receptor and several hydroxy-N-{[2-(4-phenylpiperazin-1-yl)ethyl]phenyl}nicotinamides
VL  - 79
IS  - 12
SP  - 1461
EP  - 1467
DO  - 10.2298/JSC140423070S
ER  - 

@article{
author = "Šukalović, Vladimir and Šoškić, Vukić and Ignjatović, Đurđica S. and Andrić, Deana and Penjišević, Jelena and Kostić Rajačić, Slađana",
year = "2014",
abstract = "The dopaminergic receptor system has been the focus for the development of new pharmacotherapeutic agents targeting a number of central nervous system related disorders, such as drug addiction, schizophrenia, depression, and Parkinson's disease, to name just a few. To date, the crystal structure for the human D2 receptor is not known, despite its vital function and importance as a therapeutic target. Herein, a recent advancement in the determination of key receptor ligand interactions for the available arylpiperazine-like ligands, using a D2 receptor model based on the crystal structure of the D3 receptor is presented. To determine key interactions responsible for high dopaminergic activity, computer-docking analysis was used together with experimental data. A total of 4 dopaminergic ligands showing moderate to high affinity were tested and the obtained results rationalized using ligand structures docked into the proposed D2 receptor model.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Investigation of key interactions between the second extracellular loop of the dopamine D2 receptor and several hydroxy-N-{[2-(4-phenylpiperazin-1-yl)ethyl]phenyl}nicotinamides",
volume = "79",
number = "12",
pages = "1461-1467",
doi = "10.2298/JSC140423070S"
}

Šukalović, V., Šoškić, V., Ignjatović, Đ. S., Andrić, D., Penjišević, J.,& Kostić Rajačić, S.. (2014). Investigation of key interactions between the second extracellular loop of the dopamine D2 receptor and several hydroxy-N-{[2-(4-phenylpiperazin-1-yl)ethyl]phenyl}nicotinamides. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 79(12), 1461-1467.
https://doi.org/10.2298/JSC140423070S

Šukalović V, Šoškić V, Ignjatović ĐS, Andrić D, Penjišević J, Kostić Rajačić S. Investigation of key interactions between the second extracellular loop of the dopamine D2 receptor and several hydroxy-N-{[2-(4-phenylpiperazin-1-yl)ethyl]phenyl}nicotinamides. in Journal of the Serbian Chemical Society. 2014;79(12):1461-1467.
doi:10.2298/JSC140423070S .

Šukalović, Vladimir, Šoškić, Vukić, Ignjatović, Đurđica S., Andrić, Deana, Penjišević, Jelena, Kostić Rajačić, Slađana, "Investigation of key interactions between the second extracellular loop of the dopamine D2 receptor and several hydroxy-N-{[2-(4-phenylpiperazin-1-yl)ethyl]phenyl}nicotinamides" in Journal of the Serbian Chemical Society, 79, no. 12 (2014):1461-1467,
https://doi.org/10.2298/JSC140423070S . .