TY  - JOUR
AU  - Penjišević, Jelena 
AU  - Šukalović, Vladimir 
AU  - Andrić, Deana
AU  - Suručić, Relja
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35507251
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5181
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  - DATA
AU  - Penjišević, Jelena 
AU  - Šukalović, Vladimir 
AU  - Andrić, Deana
AU  - Suručić, Relja
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5182
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  - Supplementary information for the article: Penjišević, J. Z.; Šukalović, V. B.; Andrić, D. B.; Suručić, R.; Kostić-Rajačić, S. V. 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. Applied Biochemistry and Biotechnology 2022. https://doi.org/10.1007/s12010-022-03922-8.
UR  - https://hdl.handle.net/21.15107/rcub_cherry_5182
ER  - 

@misc{
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 = "Supplementary information for the article: Penjišević, J. Z.; Šukalović, V. B.; Andrić, D. B.; Suručić, R.; Kostić-Rajačić, S. V. 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. Applied Biochemistry and Biotechnology 2022. https://doi.org/10.1007/s12010-022-03922-8.",
url = "https://hdl.handle.net/21.15107/rcub_cherry_5182"
}

Penjišević, J., Šukalović, V., Andrić, D., Suručić, R.,& Kostić-Rajačić, S.. (2022). Supplementary information for the article: Penjišević, J. Z.; Šukalović, V. B.; Andrić, D. B.; Suručić, R.; Kostić-Rajačić, S. V. 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. Applied Biochemistry and Biotechnology 2022. https://doi.org/10.1007/s12010-022-03922-8.. in Applied Biochemistry and Biotechnology
Springer..
https://hdl.handle.net/21.15107/rcub_cherry_5182

Penjišević J, Šukalović V, Andrić D, Suručić R, Kostić-Rajačić S. Supplementary information for the article: Penjišević, J. Z.; Šukalović, V. B.; Andrić, D. B.; Suručić, R.; Kostić-Rajačić, S. V. 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. Applied Biochemistry and Biotechnology 2022. https://doi.org/10.1007/s12010-022-03922-8.. in Applied Biochemistry and Biotechnology. 2022;.
https://hdl.handle.net/21.15107/rcub_cherry_5182 .

Penjišević, Jelena , Šukalović, Vladimir , Andrić, Deana, Suručić, Relja, Kostić-Rajačić, Slađana, "Supplementary information for the article: Penjišević, J. Z.; Šukalović, V. B.; Andrić, D. B.; Suručić, R.; Kostić-Rajačić, S. V. 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. Applied Biochemistry and Biotechnology 2022. https://doi.org/10.1007/s12010-022-03922-8." in Applied Biochemistry and Biotechnology (2022),
https://hdl.handle.net/21.15107/rcub_cherry_5182 .

TY  - CONF
AU  - Andrić, Deana
AU  - Dukić-Stefanović, Sladjana
AU  - Penjišević, Jelena 
AU  - Jevtić, Ivana I.
AU  - Šukalović, Vladimir 
AU  - Suručić, Relja
AU  - Kostić-Rajačić, Sladjana V.
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5282
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.
C3  - 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021
T1  - Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
DO  - 10.46793/ICCBI21.355A
ER  - 

@conference{
author = "Andrić, Deana and Dukić-Stefanović, Sladjana and Penjišević, Jelena  and Jevtić, Ivana I. and Šukalović, Vladimir  and Suručić, Relja and Kostić-Rajačić, Sladjana V.",
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.",
journal = "1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021",
title = "Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides",
doi = "10.46793/ICCBI21.355A"
}

Andrić, D., Dukić-Stefanović, S., Penjišević, J., Jevtić, I. I., Šukalović, V., Suručić, R.,& Kostić-Rajačić, S. V.. (2021). Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021.
https://doi.org/10.46793/ICCBI21.355A

Andrić D, Dukić-Stefanović S, Penjišević J, Jevtić II, Šukalović V, Suručić R, Kostić-Rajačić SV. Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021. 2021;.
doi:10.46793/ICCBI21.355A .

Andrić, Deana, Dukić-Stefanović, Sladjana, Penjišević, Jelena , Jevtić, Ivana I., Šukalović, Vladimir , Suručić, Relja, Kostić-Rajačić, Sladjana V., "Design, synthesis and pharmacological evaluation of N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in 1st International Conference on Chemo and BioInformatics (ICCBIKG 2021), Kragujevac, Serbia, 26-27th October 2021 (2021),
https://doi.org/10.46793/ICCBI21.355A . .