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  - 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  - 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  - 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  - 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  - 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  - 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 . .

TY  - JOUR
AU  - Vasić, Vesna P.
AU  - Penjišević, Jelena
AU  - Novaković, Irena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1511
AB  - A series of eight novel 5-substituted derivatives of benzimidazole was synthesized by condensation of the corresponding diamine with ethyl 4-[4-(2-chlorophenyl)piperazin-1-yl]butanoate in refluxing 4 M hydrochloric acid. In vitro antibacterial activity against ten strains, namely Bacillus subtilis, Clostridium sporogenes, Streptosporangium longisporum, Micrococcus flavus, Sarcina lutea, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Proteus vulgaris and antifungal activity against two fungal strains, namely Candida albicans and Saccharomyces cerevisiae, were evaluated. Of all the compounds screened for activity, 2-{3-[4-(2-chlorophenyl)piperazin-1-yl]propyl}-5-iodo-1H-benzimidazole and 2-{3-[4-(2-chlorophenyl)piperazin-1-yl]propyl}-5-methyl-1H-benzimidazole were associated with higher antifungal activity than commercial drugs.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole
VL  - 79
IS  - 3
SP  - 277
EP  - 282
DO  - 10.2298/JSC130418058V
ER  - 

@article{
author = "Vasić, Vesna P. and Penjišević, Jelena and Novaković, Irena and Šukalović, Vladimir and Andrić, Deana and Kostić Rajačić, Slađana",
year = "2014",
abstract = "A series of eight novel 5-substituted derivatives of benzimidazole was synthesized by condensation of the corresponding diamine with ethyl 4-[4-(2-chlorophenyl)piperazin-1-yl]butanoate in refluxing 4 M hydrochloric acid. In vitro antibacterial activity against ten strains, namely Bacillus subtilis, Clostridium sporogenes, Streptosporangium longisporum, Micrococcus flavus, Sarcina lutea, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Proteus vulgaris and antifungal activity against two fungal strains, namely Candida albicans and Saccharomyces cerevisiae, were evaluated. Of all the compounds screened for activity, 2-{3-[4-(2-chlorophenyl)piperazin-1-yl]propyl}-5-iodo-1H-benzimidazole and 2-{3-[4-(2-chlorophenyl)piperazin-1-yl]propyl}-5-methyl-1H-benzimidazole were associated with higher antifungal activity than commercial drugs.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole",
volume = "79",
number = "3",
pages = "277-282",
doi = "10.2298/JSC130418058V"
}

Vasić, V. P., Penjišević, J., Novaković, I., Šukalović, V., Andrić, D.,& Kostić Rajačić, S.. (2014). Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 79(3), 277-282.
https://doi.org/10.2298/JSC130418058V

Vasić VP, Penjišević J, Novaković I, Šukalović V, Andrić D, Kostić Rajačić S. Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole. in Journal of the Serbian Chemical Society. 2014;79(3):277-282.
doi:10.2298/JSC130418058V .

Vasić, Vesna P., Penjišević, Jelena, Novaković, Irena, Šukalović, Vladimir, Andrić, Deana, Kostić Rajačić, Slađana, "Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole" in Journal of the Serbian Chemical Society, 79, no. 3 (2014):277-282,
https://doi.org/10.2298/JSC130418058V . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Senćanski, Milan
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1349
AB  - Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately-as is true of most GPCRs-no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.
PB  - Springer, New York
T2  - Journal of Molecular Modeling
T1  - Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model
VL  - 19
IS  - 4
SP  - 1751
EP  - 1762
DO  - 10.1007/s00894-012-1731-6
ER  - 

@article{
author = "Šukalović, Vladimir and Šoškić, Vukić and Senćanski, Milan and Andrić, Deana and Kostić Rajačić, Slađana",
year = "2013",
abstract = "Interest in structure-based G-protein-coupled receptor (GPCR) ligand discovery is huge, given that almost 30 % of all approved drugs belong to this category of active compounds. The GPCR family includes the dopamine receptor subtype D2 (D2DR), but unfortunately-as is true of most GPCRs-no experimental structures are available for these receptors. In this publication, we present the molecular model of D2DR based on the previously published crystal structure of the dopamine D3 receptor (D3DR). A molecular modeling study using homology modeling and docking simulation provided a rational explanation for the behavior of the arylpiperazine ligand. The observed binding modes and receptor-ligand interactions provided us with fresh clues about how to optimize selectivity for D2DR receptors.",
publisher = "Springer, New York",
journal = "Journal of Molecular Modeling",
title = "Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model",
volume = "19",
number = "4",
pages = "1751-1762",
doi = "10.1007/s00894-012-1731-6"
}

Šukalović, V., Šoškić, V., Senćanski, M., Andrić, D.,& Kostić Rajačić, S.. (2013). Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model. in Journal of Molecular Modeling
Springer, New York., 19(4), 1751-1762.
https://doi.org/10.1007/s00894-012-1731-6

Šukalović V, Šoškić V, Senćanski M, Andrić D, Kostić Rajačić S. Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model. in Journal of Molecular Modeling. 2013;19(4):1751-1762.
doi:10.1007/s00894-012-1731-6 .

Šukalović, Vladimir, Šoškić, Vukić, Senćanski, Milan, Andrić, Deana, Kostić Rajačić, Slađana, "Determination of key receptor-ligand interactions of dopaminergic arylpiperazines and the dopamine D2 receptor homology model" in Journal of Molecular Modeling, 19, no. 4 (2013):1751-1762,
https://doi.org/10.1007/s00894-012-1731-6 . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Bogdan, Anca Elena
AU  - Tovilović, Gordana
AU  - Ignjatović, Đurđica S.
AU  - Andrić, Deana
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2013
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1193
AB  - The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv der Pharmazie
T1  - N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling
VL  - 346
IS  - 10
SP  - 708
EP  - 717
DO  - 10.1002/ardp.201300189
ER  - 

@article{
author = "Šukalović, Vladimir and Bogdan, Anca Elena and Tovilović, Gordana and Ignjatović, Đurđica S. and Andrić, Deana and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2013",
abstract = "The ratio of affinities toward the dopamine D-2 and the 5-hydroxytryptamine 5-HT1A receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D-2 and 5-hydroxytryptamine 5-HT1A receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D-2/5-HT1A profile.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv der Pharmazie",
title = "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling",
volume = "346",
number = "10",
pages = "708-717",
doi = "10.1002/ardp.201300189"
}

Šukalović, V., Bogdan, A. E., Tovilović, G., Ignjatović, Đ. S., Andrić, D., Kostić Rajačić, S.,& Šoškić, V.. (2013). N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 346(10), 708-717.
https://doi.org/10.1002/ardp.201300189

Šukalović V, Bogdan AE, Tovilović G, Ignjatović ĐS, Andrić D, Kostić Rajačić S, Šoškić V. N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling. in Archiv der Pharmazie. 2013;346(10):708-717.
doi:10.1002/ardp.201300189 .

Šukalović, Vladimir, Bogdan, Anca Elena, Tovilović, Gordana, Ignjatović, Đurđica S., Andrić, Deana, Kostić Rajačić, Slađana, Šoškić, Vukić, "N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with Dopamine D-2 and 5-Hydroxytryptamine 5HT(1A) Activity: Synthesis, Testing, and Molecular Modeling" in Archiv der Pharmazie, 346, no. 10 (2013):708-717,
https://doi.org/10.1002/ardp.201300189 . .

TY  - JOUR
AU  - Senćanski, Milan V.
AU  - Šukalović, Vladimir
AU  - Došen-Mićović, Ljiljana
AU  - Šoškić, Vukić
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1057
AB  - Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with alpha(1A) adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of alpha(1A) adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.
PB  - Inst Materials Physics, Bucharest
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands
VL  - 7
IS  - 4
SP  - 1767
EP  - 1777
UR  - https://hdl.handle.net/21.15107/rcub_cherry_1567
ER  - 

@article{
author = "Senćanski, Milan V. and Šukalović, Vladimir and Došen-Mićović, Ljiljana and Šoškić, Vukić and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with alpha(1A) adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of alpha(1A) adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.",
publisher = "Inst Materials Physics, Bucharest",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands",
volume = "7",
number = "4",
pages = "1767-1777",
url = "https://hdl.handle.net/21.15107/rcub_cherry_1567"
}

Senćanski, M. V., Šukalović, V., Došen-Mićović, L., Šoškić, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures
Inst Materials Physics, Bucharest., 7(4), 1767-1777.
https://hdl.handle.net/21.15107/rcub_cherry_1567

Senćanski MV, Šukalović V, Došen-Mićović L, Šoškić V, Andrić D, Roglić G, Kostić Rajačić S. Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures. 2012;7(4):1767-1777.
https://hdl.handle.net/21.15107/rcub_cherry_1567 .

Senćanski, Milan V., Šukalović, Vladimir, Došen-Mićović, Ljiljana, Šoškić, Vukić, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands" in Digest Journal of Nanomaterials and Biostructures, 7, no. 4 (2012):1767-1777,
https://hdl.handle.net/21.15107/rcub_cherry_1567 .

TY  - JOUR
AU  - Senćanski, Milan V.
AU  - Šukalović, Vladimir
AU  - Došen-Mićović, Ljiljana
AU  - Šoškić, Vukić
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1146
AB  - Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with α1A adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of α1A adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.
PB  - Inst Materials Physics, Bucharest
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands
VL  - 7
IS  - 4
SP  - 1761
EP  - 1777
UR  - https://hdl.handle.net/21.15107/rcub_cherry_112
ER  - 

@article{
author = "Senćanski, Milan V. and Šukalović, Vladimir and Došen-Mićović, Ljiljana and Šoškić, Vukić and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with α1A adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of α1A adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.",
publisher = "Inst Materials Physics, Bucharest",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands",
volume = "7",
number = "4",
pages = "1761-1777",
url = "https://hdl.handle.net/21.15107/rcub_cherry_112"
}

Senćanski, M. V., Šukalović, V., Došen-Mićović, L., Šoškić, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures
Inst Materials Physics, Bucharest., 7(4), 1761-1777.
https://hdl.handle.net/21.15107/rcub_cherry_112

Senćanski MV, Šukalović V, Došen-Mićović L, Šoškić V, Andrić D, Roglić G, Kostić Rajačić S. Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures. 2012;7(4):1761-1777.
https://hdl.handle.net/21.15107/rcub_cherry_112 .

Senćanski, Milan V., Šukalović, Vladimir, Došen-Mićović, Ljiljana, Šoškić, Vukić, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands" in Digest Journal of Nanomaterials and Biostructures, 7, no. 4 (2012):1761-1777,
https://hdl.handle.net/21.15107/rcub_cherry_112 .

TY  - JOUR
AU  - Ignjatović, Đurđica S.
AU  - Milutinovic, Danijela Vojnovic
AU  - Nikolić-Kokić, Aleksandra
AU  - Slavic, Marija
AU  - Andrić, Deana
AU  - Tomić, Mirko
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/955
AB  - A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity.
PB  - Elsevier
T2  - European Journal of Pharmacology
T1  - The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside
VL  - 683
IS  - 1-3
SP  - 93
EP  - 100
DO  - 10.1016/j.ejphar.2012.03.011
ER  - 

@article{
author = "Ignjatović, Đurđica S. and Milutinovic, Danijela Vojnovic and Nikolić-Kokić, Aleksandra and Slavic, Marija and Andrić, Deana and Tomić, Mirko and Kostić Rajačić, Slađana",
year = "2012",
abstract = "A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity.",
publisher = "Elsevier",
journal = "European Journal of Pharmacology",
title = "The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside",
volume = "683",
number = "1-3",
pages = "93-100",
doi = "10.1016/j.ejphar.2012.03.011"
}

Ignjatović, Đ. S., Milutinovic, D. V., Nikolić-Kokić, A., Slavic, M., Andrić, D., Tomić, M.,& Kostić Rajačić, S.. (2012). The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside. in European Journal of Pharmacology
Elsevier., 683(1-3), 93-100.
https://doi.org/10.1016/j.ejphar.2012.03.011

Ignjatović ĐS, Milutinovic DV, Nikolić-Kokić A, Slavic M, Andrić D, Tomić M, Kostić Rajačić S. The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside. in European Journal of Pharmacology. 2012;683(1-3):93-100.
doi:10.1016/j.ejphar.2012.03.011 .

Ignjatović, Đurđica S., Milutinovic, Danijela Vojnovic, Nikolić-Kokić, Aleksandra, Slavic, Marija, Andrić, Deana, Tomić, Mirko, Kostić Rajačić, Slađana, "The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside" in European Journal of Pharmacology, 683, no. 1-3 (2012):93-100,
https://doi.org/10.1016/j.ejphar.2012.03.011 . .

TY  - JOUR
AU  - Novaković, Irena
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/963
AB  - The derivatives of cinnamic acid and N-arylpiperazine show antibacterial activity. In this work the potential synergistic effect of cinnamyl derivatives of arylpiperazine in selected bacteria was investigated. The antibacterial activities of the derivatives were evaluated against Gram-positive bacteria: Staphylococcus aureus, Streptosporangium longisporum, Sarcina lutea, Micrococcus flavus, Clostridium sporogenes and Bacillus subtilis and Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Proteus vulgaris by the disc diffusion method. The minimum inhibitory concentration (MIC) against the selected bacteria was determined for all compounds that showed activity in the disc diffusion method. The majority of the investigated compounds displayed in vitro antibacterial activity. The effect of the type and structure of the substituent on the aromatic ring on the antibacterial activity is discussed. It was found that two derivatives expressed activity toward S. longisporum and P. aeruginosa that was almost as strong as that of amikacin.
PB  - Inst Bioloska Istrazivanja Sinisa Stankovic, Beograd
T2  - Archives of Biological Sciences
T1  - Investigation of antibacterial activity of cinnamyl derivatives of arylpiperazine
VL  - 64
IS  - 1
SP  - 15
EP  - 20
DO  - 10.2298/ABS1201015N
ER  - 

@article{
author = "Novaković, Irena and Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "The derivatives of cinnamic acid and N-arylpiperazine show antibacterial activity. In this work the potential synergistic effect of cinnamyl derivatives of arylpiperazine in selected bacteria was investigated. The antibacterial activities of the derivatives were evaluated against Gram-positive bacteria: Staphylococcus aureus, Streptosporangium longisporum, Sarcina lutea, Micrococcus flavus, Clostridium sporogenes and Bacillus subtilis and Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Proteus vulgaris by the disc diffusion method. The minimum inhibitory concentration (MIC) against the selected bacteria was determined for all compounds that showed activity in the disc diffusion method. The majority of the investigated compounds displayed in vitro antibacterial activity. The effect of the type and structure of the substituent on the aromatic ring on the antibacterial activity is discussed. It was found that two derivatives expressed activity toward S. longisporum and P. aeruginosa that was almost as strong as that of amikacin.",
publisher = "Inst Bioloska Istrazivanja Sinisa Stankovic, Beograd",
journal = "Archives of Biological Sciences",
title = "Investigation of antibacterial activity of cinnamyl derivatives of arylpiperazine",
volume = "64",
number = "1",
pages = "15-20",
doi = "10.2298/ABS1201015N"
}

Novaković, I., Penjišević, J., Šukalović, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Investigation of antibacterial activity of cinnamyl derivatives of arylpiperazine. in Archives of Biological Sciences
Inst Bioloska Istrazivanja Sinisa Stankovic, Beograd., 64(1), 15-20.
https://doi.org/10.2298/ABS1201015N

Novaković I, Penjišević J, Šukalović V, Andrić D, Roglić G, Kostić Rajačić S. Investigation of antibacterial activity of cinnamyl derivatives of arylpiperazine. in Archives of Biological Sciences. 2012;64(1):15-20.
doi:10.2298/ABS1201015N .

Novaković, Irena, Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Investigation of antibacterial activity of cinnamyl derivatives of arylpiperazine" in Archives of Biological Sciences, 64, no. 1 (2012):15-20,
https://doi.org/10.2298/ABS1201015N . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Ignjatović, Đurđica S.
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Shakib, Kaveh
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/974
AB  - It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors
VL  - 22
IS  - 12
SP  - 3967
EP  - 3972
DO  - 10.1016/j.bmcl.2012.04.098
ER  - 

@article{
author = "Šukalović, Vladimir and Ignjatović, Đurđica S. and Tovilović, Gordana and Andrić, Deana and Shakib, Kaveh and Kostić Rajačić, Slađana and Šoškić, Vukić",
year = "2012",
abstract = "It is suggested that the ratio of dopamine D-2 to 5-hydroxytryptamine 5-HT1A activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D-2 and 5-hydrohytryptamine 5-HT1A receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT1A receptors.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors",
volume = "22",
number = "12",
pages = "3967-3972",
doi = "10.1016/j.bmcl.2012.04.098"
}

Šukalović, V., Ignjatović, Đ. S., Tovilović, G., Andrić, D., Shakib, K., Kostić Rajačić, S.,& Šoškić, V.. (2012). Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters
Oxford : Pergamon-Elsevier Science Ltd., 22(12), 3967-3972.
https://doi.org/10.1016/j.bmcl.2012.04.098

Šukalović V, Ignjatović ĐS, Tovilović G, Andrić D, Shakib K, Kostić Rajačić S, Šoškić V. Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors. in Bioorganic and Medicinal Chemistry Letters. 2012;22(12):3967-3972.
doi:10.1016/j.bmcl.2012.04.098 .

Šukalović, Vladimir, Ignjatović, Đurđica S., Tovilović, Gordana, Andrić, Deana, Shakib, Kaveh, Kostić Rajačić, Slađana, Šoškić, Vukić, "Interactions of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas with dopamine D-2 and 5-hydroxytryptamine 5HT(1A) receptors" in Bioorganic and Medicinal Chemistry Letters, 22, no. 12 (2012):3967-3972,
https://doi.org/10.1016/j.bmcl.2012.04.098 . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1022
AB  - Second extracellular loop (ecl2) of the dopamine (DA) D2 receptor is an essential part of the binding pocket of dopaminergic ligands. To form a part of the ligand-binding surface, it has to fold down into the transmembrane domain of the DA receptor. The current study describes the modeling of the D2 DA receptor ecl2 and its interactions with arylpiperazine ligands. In order to model the D2 DA receptor ecl2, several arylpiperazine ligands were used to propose a pharmacophore model. D2 DA receptor ecl2 model was built using Accelrys Discovery Studio. To test the proposed model, docking analysis was performed and key amino acid residues were determined. The proposed receptor-ligand interactions were rationalized and compared with measured binding affinities. It is shown that D2 DA receptor ecl2 significantly participates in the formation of the receptor-ligand complex through aromatic, hydrophobic and polar interaction. Considering them would benefit molecular modeling of G- protein-coupled receptors (GPCRs) and facilitate the design of novel active compounds.
AB  - Druga ekstracelularna petlja dopaminskog D2 receptora je esencijalni deo vezivnog mesta receptora. Da bi se definisala gornja strana vezivnog mesta, ona mora da se savije nadole, i orijentiše ka transmembranskom domenu receptora. U ovom radu opisan je proces modelovanja druge ekstracelularne petlje dopaminskog D2 receptora i njene interakcije sa arilpiperazinskim ligandima. Za modelovanje je korišćen Accelrys Discovery Studio paket programa. Predloženi model je testiran doking analizom literaturno dostupnih liganada i poređenjem dobijenih rezultata sa njihovim afinitetom vezivanja za D2 receptor. Određeni su amino-kiselinski ostaci koji stupaju u interakcije sa ligandima. Ključne interakcije su definisane i upoređene sa afinitetima liganada prema receptoru kako bi se predloženim modelom objasnile razlike u eksperimentalnim rezultatima. Naša istraživanja su pokazala da druga ekstracelularna petlja dopaminskog D2 receptora može stupati u različite interakcije sa arilpiperazinskim ligandima koje između ostalih uključuju hidrofobne, aromatične interakcije ali i vodnonične veze. Ova saznanja, u kombinaciji sa predloženim modelom D2 receptora, koji uključuje ekstracelularne petlje, mogu biti od velike koristi prilikom budućeg dizajna novih dopaminergičkih liganada.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Modeling key interactions between the second extracellular loop of the dopamine D2 receptor and arylpiperazine ligands
T1  - Modelovanje ključnih interakcija između druge ekstracelularne petlje dopaminskog D2 receptora i arilpiperazina kao liganada
VL  - 77
IS  - 3
SP  - 259
EP  - 277
DO  - 10.2298/JSC111028212S
ER  - 

@article{
author = "Šukalović, Vladimir and Šoškić, Vukić and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "Second extracellular loop (ecl2) of the dopamine (DA) D2 receptor is an essential part of the binding pocket of dopaminergic ligands. To form a part of the ligand-binding surface, it has to fold down into the transmembrane domain of the DA receptor. The current study describes the modeling of the D2 DA receptor ecl2 and its interactions with arylpiperazine ligands. In order to model the D2 DA receptor ecl2, several arylpiperazine ligands were used to propose a pharmacophore model. D2 DA receptor ecl2 model was built using Accelrys Discovery Studio. To test the proposed model, docking analysis was performed and key amino acid residues were determined. The proposed receptor-ligand interactions were rationalized and compared with measured binding affinities. It is shown that D2 DA receptor ecl2 significantly participates in the formation of the receptor-ligand complex through aromatic, hydrophobic and polar interaction. Considering them would benefit molecular modeling of G- protein-coupled receptors (GPCRs) and facilitate the design of novel active compounds., Druga ekstracelularna petlja dopaminskog D2 receptora je esencijalni deo vezivnog mesta receptora. Da bi se definisala gornja strana vezivnog mesta, ona mora da se savije nadole, i orijentiše ka transmembranskom domenu receptora. U ovom radu opisan je proces modelovanja druge ekstracelularne petlje dopaminskog D2 receptora i njene interakcije sa arilpiperazinskim ligandima. Za modelovanje je korišćen Accelrys Discovery Studio paket programa. Predloženi model je testiran doking analizom literaturno dostupnih liganada i poređenjem dobijenih rezultata sa njihovim afinitetom vezivanja za D2 receptor. Određeni su amino-kiselinski ostaci koji stupaju u interakcije sa ligandima. Ključne interakcije su definisane i upoređene sa afinitetima liganada prema receptoru kako bi se predloženim modelom objasnile razlike u eksperimentalnim rezultatima. Naša istraživanja su pokazala da druga ekstracelularna petlja dopaminskog D2 receptora može stupati u različite interakcije sa arilpiperazinskim ligandima koje između ostalih uključuju hidrofobne, aromatične interakcije ali i vodnonične veze. Ova saznanja, u kombinaciji sa predloženim modelom D2 receptora, koji uključuje ekstracelularne petlje, mogu biti od velike koristi prilikom budućeg dizajna novih dopaminergičkih liganada.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Modeling key interactions between the second extracellular loop of the dopamine D2 receptor and arylpiperazine ligands, Modelovanje ključnih interakcija između druge ekstracelularne petlje dopaminskog D2 receptora i arilpiperazina kao liganada",
volume = "77",
number = "3",
pages = "259-277",
doi = "10.2298/JSC111028212S"
}

Šukalović, V., Šoškić, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Modeling key interactions between the second extracellular loop of the dopamine D2 receptor and arylpiperazine ligands. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 77(3), 259-277.
https://doi.org/10.2298/JSC111028212S

Šukalović V, Šoškić V, Andrić D, Roglić G, Kostić Rajačić S. Modeling key interactions between the second extracellular loop of the dopamine D2 receptor and arylpiperazine ligands. in Journal of the Serbian Chemical Society. 2012;77(3):259-277.
doi:10.2298/JSC111028212S .

Šukalović, Vladimir, Šoškić, Vukić, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Modeling key interactions between the second extracellular loop of the dopamine D2 receptor and arylpiperazine ligands" in Journal of the Serbian Chemical Society, 77, no. 3 (2012):259-277,
https://doi.org/10.2298/JSC111028212S . .

TY  - JOUR
AU  - Tomić, Mirko
AU  - Vasković, Djurdjica
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić Rajačić, Slađana
PY  - 2011
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/916
AB  - Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D-2, 5-HT2A, and alpha(1)-adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with brominemay greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT2A/D-2 pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl) phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.
PB  - Wiley-Blackwell, Malden
T2  - Archiv der Pharmazie
T1  - Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands
VL  - 344
IS  - 5
SP  - 287
EP  - 291
DO  - 10.1002/ardp.200900168
ER  - 

@article{
author = "Tomić, Mirko and Vasković, Djurdjica and Tovilović, Gordana and Andrić, Deana and Penjišević, Jelena and Kostić Rajačić, Slađana",
year = "2011",
abstract = "Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D-2, 5-HT2A, and alpha(1)-adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with brominemay greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT2A/D-2 pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl) phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.",
publisher = "Wiley-Blackwell, Malden",
journal = "Archiv der Pharmazie",
title = "Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands",
volume = "344",
number = "5",
pages = "287-291",
doi = "10.1002/ardp.200900168"
}

Tomić, M., Vasković, D., Tovilović, G., Andrić, D., Penjišević, J.,& Kostić Rajačić, S.. (2011). Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands. in Archiv der Pharmazie
Wiley-Blackwell, Malden., 344(5), 287-291.
https://doi.org/10.1002/ardp.200900168

Tomić M, Vasković D, Tovilović G, Andrić D, Penjišević J, Kostić Rajačić S. Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands. in Archiv der Pharmazie. 2011;344(5):287-291.
doi:10.1002/ardp.200900168 .

Tomić, Mirko, Vasković, Djurdjica, Tovilović, Gordana, Andrić, Deana, Penjišević, Jelena, Kostić Rajačić, Slađana, "Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D-2 and 5-HT2A Receptor Ligands" in Archiv der Pharmazie, 344, no. 5 (2011):287-291,
https://doi.org/10.1002/ardp.200900168 . .

TY  - JOUR
AU  - Šukalović, Vladimir
AU  - Zlatović, Mario
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
AU  - Andrić, Deana
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/494
AB  - Our previously described research on docking analysis of a series of isosteric N4-arylpiperazines on a model of 5-HT1A receptor was used earlier to investigate interactions of different ligands with the receptor binding site. Due to the limitations of molecular mechanics (MM) methods, docking analysis failed to give precise results about interactions that influence binding affinity of the ligands, but we presumed that aromatic-aromatic interactions, or edge-to-face, to be more precise, play an important role in the binding process. In order to further elaborate on this hypothesis, ab initio approach was used to calculate possible edge-to-face interactions on a model system and correlate them to ligand affinity. Obtained results indicate that those dispersive interactions can show notable influence on the binding of the ligands to 5-HT1A receptor. Stabilization energies of modeled receptor-ligand complex, calculated using Becke's "half-and-half" hybrid DFT method showed strong correlation with the affinity of investigated ligands towards 5-HT1A receptor.
PB  - Slovensko Kemijsko Drustvo, Ljubljana
T2  - Acta Chimica Slovenica
T1  - Application of Hybrid Density Functional Theory in Calculation of Edge-to-Face Interactions of Receptor-Ligand System
VL  - 56
IS  - 1
SP  - 270
EP  - 277
UR  - https://hdl.handle.net/21.15107/rcub_cherry_626
ER  - 

@article{
author = "Šukalović, Vladimir and Zlatović, Mario and Roglić, Goran and Kostić Rajačić, Slađana and Andrić, Deana",
year = "2009",
abstract = "Our previously described research on docking analysis of a series of isosteric N4-arylpiperazines on a model of 5-HT1A receptor was used earlier to investigate interactions of different ligands with the receptor binding site. Due to the limitations of molecular mechanics (MM) methods, docking analysis failed to give precise results about interactions that influence binding affinity of the ligands, but we presumed that aromatic-aromatic interactions, or edge-to-face, to be more precise, play an important role in the binding process. In order to further elaborate on this hypothesis, ab initio approach was used to calculate possible edge-to-face interactions on a model system and correlate them to ligand affinity. Obtained results indicate that those dispersive interactions can show notable influence on the binding of the ligands to 5-HT1A receptor. Stabilization energies of modeled receptor-ligand complex, calculated using Becke's "half-and-half" hybrid DFT method showed strong correlation with the affinity of investigated ligands towards 5-HT1A receptor.",
publisher = "Slovensko Kemijsko Drustvo, Ljubljana",
journal = "Acta Chimica Slovenica",
title = "Application of Hybrid Density Functional Theory in Calculation of Edge-to-Face Interactions of Receptor-Ligand System",
volume = "56",
number = "1",
pages = "270-277",
url = "https://hdl.handle.net/21.15107/rcub_cherry_626"
}

Šukalović, V., Zlatović, M., Roglić, G., Kostić Rajačić, S.,& Andrić, D.. (2009). Application of Hybrid Density Functional Theory in Calculation of Edge-to-Face Interactions of Receptor-Ligand System. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo, Ljubljana., 56(1), 270-277.
https://hdl.handle.net/21.15107/rcub_cherry_626

Šukalović V, Zlatović M, Roglić G, Kostić Rajačić S, Andrić D. Application of Hybrid Density Functional Theory in Calculation of Edge-to-Face Interactions of Receptor-Ligand System. in Acta Chimica Slovenica. 2009;56(1):270-277.
https://hdl.handle.net/21.15107/rcub_cherry_626 .

Šukalović, Vladimir, Zlatović, Mario, Roglić, Goran, Kostić Rajačić, Slađana, Andrić, Deana, "Application of Hybrid Density Functional Theory in Calculation of Edge-to-Face Interactions of Receptor-Ligand System" in Acta Chimica Slovenica, 56, no. 1 (2009):270-277,
https://hdl.handle.net/21.15107/rcub_cherry_626 .