TY  - JOUR
AU  - Tomic, Mirko
AU  - Vaskovic, Djurdjica
AU  - Tovilović, Gordana
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1337
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 = "Tomic, Mirko and Vaskovic, 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"
}

Tomic, M., Vaskovic, 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

Tomic M, Vaskovic 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 .

Tomic, Mirko, Vaskovic, 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  - Zlatović, Mario
AU  - Šukalović, Vladimir
AU  - Roglić, Goran
AU  - Kostić-Rajačić, Slađana
AU  - Andrić, Deana
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1018
AB  - Several isosteric 1,3-dihydro-5-[2-(4-aryl-l-piperazinyl)ethyl]-2H-benzinlidazole-2-thiones were used to investigate the interactions of different ligands with the binding site of the D2 receptor. Due to limitations of the simulation methods, docking analysis failed to show precisely the interactions that influence the binding affinity of the ligands. It is presumed that dispersive forces or more precisely edge-to-face interactions play an important role in the binding process, especially for the lipophilic part of the ligands. In order to confirm this hypothesis, ab initio calculations were applied on a model system in order to find the stabilization energies of potential edge-to-face interactions and then to correlate them with the ligand affinity. The obtained results indicate that there is a significant correlation between the strength of dispersive interactions and ligand affinity. It was shown that for the calculation of stabilization energies of modeled receptor-ligand complexes the Becke "half-and-half" hybrid DFT method can be used, thus speeding up the usually long calculation time and reducing the required computer strength.
AB  - Nekoliko izosternih 1,3-dihidro-5-[2-(4-aril-1-piperazinil)etil]-2H-benzimidazol-2-tiona je korišćeno da bi se ispitale interakcije različitih liganada sa vezivnim mestom dopaminskog D2 receptora. Zbog ograničenja metoda korišćenih za simulaciju vezivanja, analiza ovih rezultata nije mogla da pokaže preciznije koje interakcije utiču na afinitet vezivanja liganada. Pretpostavljeno je da disperzivne sile, ili preciznije, tzv. edge-to-face interakcije, igraju značajnu ulogu u procesu vezivanja, naročito u lipofilnom delu liganda. Da bi se potvrdila ova hipoteza primenom ab initio izračunavanja na model sistem, pokušano je izračunavanje stabilizacione energije ovih interakcija i njeno dovođenje u vezu sa afinitetom liganada. Dobijeni rezultati ukazuju da postoji značajna korelacija između jačine disperzivnih interakcija i afiniteta liganda. Pokazano je da se pri izračunavanju stabilizacionih energija modelovanih kompleksa ligand-receptor može upotrebiti Beckeova 'half-and-half' hibridna DFT metoda, što značajno smanjuje vreme potrebno za izračunavanja i potrebne računarske resurse.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - The influence of dispersive interactions on the binding affinities of ligands with an arylpiperazine moiety to the dopamine D2 receptor
T1  - Uticaj disperzivnih interakcija na afinitet vezivanja liganada sa arilpiperazinskom funkcijom za dopaminski D2 receptor
VL  - 74
IS  - 10
SP  - 1051
EP  - 1061
DO  - 10.2298/JSC0910051Z
ER  - 

@article{
author = "Zlatović, Mario and Šukalović, Vladimir and Roglić, Goran and Kostić-Rajačić, Slađana and Andrić, Deana",
year = "2009",
abstract = "Several isosteric 1,3-dihydro-5-[2-(4-aryl-l-piperazinyl)ethyl]-2H-benzinlidazole-2-thiones were used to investigate the interactions of different ligands with the binding site of the D2 receptor. Due to limitations of the simulation methods, docking analysis failed to show precisely the interactions that influence the binding affinity of the ligands. It is presumed that dispersive forces or more precisely edge-to-face interactions play an important role in the binding process, especially for the lipophilic part of the ligands. In order to confirm this hypothesis, ab initio calculations were applied on a model system in order to find the stabilization energies of potential edge-to-face interactions and then to correlate them with the ligand affinity. The obtained results indicate that there is a significant correlation between the strength of dispersive interactions and ligand affinity. It was shown that for the calculation of stabilization energies of modeled receptor-ligand complexes the Becke "half-and-half" hybrid DFT method can be used, thus speeding up the usually long calculation time and reducing the required computer strength., Nekoliko izosternih 1,3-dihidro-5-[2-(4-aril-1-piperazinil)etil]-2H-benzimidazol-2-tiona je korišćeno da bi se ispitale interakcije različitih liganada sa vezivnim mestom dopaminskog D2 receptora. Zbog ograničenja metoda korišćenih za simulaciju vezivanja, analiza ovih rezultata nije mogla da pokaže preciznije koje interakcije utiču na afinitet vezivanja liganada. Pretpostavljeno je da disperzivne sile, ili preciznije, tzv. edge-to-face interakcije, igraju značajnu ulogu u procesu vezivanja, naročito u lipofilnom delu liganda. Da bi se potvrdila ova hipoteza primenom ab initio izračunavanja na model sistem, pokušano je izračunavanje stabilizacione energije ovih interakcija i njeno dovođenje u vezu sa afinitetom liganada. Dobijeni rezultati ukazuju da postoji značajna korelacija između jačine disperzivnih interakcija i afiniteta liganda. Pokazano je da se pri izračunavanju stabilizacionih energija modelovanih kompleksa ligand-receptor može upotrebiti Beckeova 'half-and-half' hibridna DFT metoda, što značajno smanjuje vreme potrebno za izračunavanja i potrebne računarske resurse.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "The influence of dispersive interactions on the binding affinities of ligands with an arylpiperazine moiety to the dopamine D2 receptor, Uticaj disperzivnih interakcija na afinitet vezivanja liganada sa arilpiperazinskom funkcijom za dopaminski D2 receptor",
volume = "74",
number = "10",
pages = "1051-1061",
doi = "10.2298/JSC0910051Z"
}

Zlatović, M., Šukalović, V., Roglić, G., Kostić-Rajačić, S.,& Andrić, D.. (2009). The influence of dispersive interactions on the binding affinities of ligands with an arylpiperazine moiety to the dopamine D2 receptor. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 74(10), 1051-1061.
https://doi.org/10.2298/JSC0910051Z

Zlatović M, Šukalović V, Roglić G, Kostić-Rajačić S, Andrić D. The influence of dispersive interactions on the binding affinities of ligands with an arylpiperazine moiety to the dopamine D2 receptor. in Journal of the Serbian Chemical Society. 2009;74(10):1051-1061.
doi:10.2298/JSC0910051Z .

Zlatović, Mario, Šukalović, Vladimir, Roglić, Goran, Kostić-Rajačić, Slađana, Andrić, Deana, "The influence of dispersive interactions on the binding affinities of ligands with an arylpiperazine moiety to the dopamine D2 receptor" in Journal of the Serbian Chemical Society, 74, no. 10 (2009):1051-1061,
https://doi.org/10.2298/JSC0910051Z . .

TY  - JOUR
AU  - Sukalović, Vladimir V.
AU  - Zlatović, Mario
AU  - Roglić, Goran
AU  - Kostić-Rajačić, Slađana
AU  - Andrić, Deana
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/626
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 = "Sukalović, Vladimir V. 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"
}

Sukalović, V. 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

Sukalović VV, 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 .

Sukalović, Vladimir V., 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 .

TY  - JOUR
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Šukalović, Vladimir
AU  - Šoškić, Vukić
AU  - Kostić-Rajačić, Slađana
PY  - 2008
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/969
AB  - In this publication we are describing synthesis, binding properties, and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, a new compounds with potential antipsychotics properties. Affinity towards the dopamine D(1)-like and D(2)-like, and serotonin 5-HT(1A) receptors was evaluated using the radioligand binding assays. All compounds tested had affinity for the D(2)-like and 5-HT(1A) receptors, but were inactive towards the D(1)-like receptor. Halogenated 6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles showed higher affinity compared to their nonhalogenated congeners. In silico docking analysis of selected ligands was performed in order to explain the results of binding assays. Our analysis suggests that stabilizing interactions between the halogen atom at the benzimidazole ring and the Ser-122 of the D(2)-like and Trp-358 of the 5-HT(1A) receptor. Energy contributions for these interactions were calculated using the ab initio method. (c) 2007 Elsevier Masson SAS. All rights reserved.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Paris
T2  - European Journal of Medicinal Chemistry
T1  - Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D(2) and 5-HT(1A) receptors
VL  - 43
IS  - 8
SP  - 1696
EP  - 1705
DO  - 10.1016/j.ejmech.2007.09.027
ER  - 

@article{
author = "Andrić, Deana and Roglić, Goran and Šukalović, Vladimir and Šoškić, Vukić and Kostić-Rajačić, Slađana",
year = "2008",
abstract = "In this publication we are describing synthesis, binding properties, and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, a new compounds with potential antipsychotics properties. Affinity towards the dopamine D(1)-like and D(2)-like, and serotonin 5-HT(1A) receptors was evaluated using the radioligand binding assays. All compounds tested had affinity for the D(2)-like and 5-HT(1A) receptors, but were inactive towards the D(1)-like receptor. Halogenated 6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles showed higher affinity compared to their nonhalogenated congeners. In silico docking analysis of selected ligands was performed in order to explain the results of binding assays. Our analysis suggests that stabilizing interactions between the halogen atom at the benzimidazole ring and the Ser-122 of the D(2)-like and Trp-358 of the 5-HT(1A) receptor. Energy contributions for these interactions were calculated using the ab initio method. (c) 2007 Elsevier Masson SAS. All rights reserved.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Paris",
journal = "European Journal of Medicinal Chemistry",
title = "Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D(2) and 5-HT(1A) receptors",
volume = "43",
number = "8",
pages = "1696-1705",
doi = "10.1016/j.ejmech.2007.09.027"
}

Andrić, D., Roglić, G., Šukalović, V., Šoškić, V.,& Kostić-Rajačić, S.. (2008). Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D(2) and 5-HT(1A) receptors. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Paris., 43(8), 1696-1705.
https://doi.org/10.1016/j.ejmech.2007.09.027

Andrić D, Roglić G, Šukalović V, Šoškić V, Kostić-Rajačić S. Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D(2) and 5-HT(1A) receptors. in European Journal of Medicinal Chemistry. 2008;43(8):1696-1705.
doi:10.1016/j.ejmech.2007.09.027 .

Andrić, Deana, Roglić, Goran, Šukalović, Vladimir, Šoškić, Vukić, Kostić-Rajačić, Slađana, "Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D(2) and 5-HT(1A) receptors" in European Journal of Medicinal Chemistry, 43, no. 8 (2008):1696-1705,
https://doi.org/10.1016/j.ejmech.2007.09.027 . .

TY  - JOUR
AU  - Tomic, Mirko
AU  - Ignjatović, Đurđica
AU  - Tovijovic, Gordana
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić-Rajačić, Slađana
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/886
AB  - Two new series of substituted arylpiperazines with heterocyclic 3-propoxy-benzimidazole or 3-propoxy-benzimidazole-2-thione groups were synthesized and their in vitro binding affinities for the D,, 5-HT1A, 5-HT2A, and alpha-adrenergic receptors determined. Among them, only two compounds with phenyl aryl-constituent (8a and 9a) showed 5-HT2A/D-2 pK(i) binding ratios proposed for atypical neuroleptics. As to their behavioral screening on rodents, both compounds exhibited a non-cataleptic action in rats and antagonized D-amphetamine-induced hyperlocomotion in mice, suggesting their possible atypical antipsychotic potency. (c) 2007 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - Two new phenylpiperazines with atypical antipsychotic potential
VL  - 17
IS  - 21
SP  - 5749
EP  - 5753
DO  - 10.1016/j.bmcl.2007.08.066
ER  - 

@article{
author = "Tomic, Mirko and Ignjatović, Đurđica and Tovijovic, Gordana and Andrić, Deana and Roglić, Goran and Kostić-Rajačić, Slađana",
year = "2007",
abstract = "Two new series of substituted arylpiperazines with heterocyclic 3-propoxy-benzimidazole or 3-propoxy-benzimidazole-2-thione groups were synthesized and their in vitro binding affinities for the D,, 5-HT1A, 5-HT2A, and alpha-adrenergic receptors determined. Among them, only two compounds with phenyl aryl-constituent (8a and 9a) showed 5-HT2A/D-2 pK(i) binding ratios proposed for atypical neuroleptics. As to their behavioral screening on rodents, both compounds exhibited a non-cataleptic action in rats and antagonized D-amphetamine-induced hyperlocomotion in mice, suggesting their possible atypical antipsychotic potency. (c) 2007 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "Two new phenylpiperazines with atypical antipsychotic potential",
volume = "17",
number = "21",
pages = "5749-5753",
doi = "10.1016/j.bmcl.2007.08.066"
}

Tomic, M., Ignjatović, Đ., Tovijovic, G., Andrić, D., Roglić, G.,& Kostić-Rajačić, S.. (2007). Two new phenylpiperazines with atypical antipsychotic potential. in Bioorganic and Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd, Oxford., 17(21), 5749-5753.
https://doi.org/10.1016/j.bmcl.2007.08.066

Tomic M, Ignjatović Đ, Tovijovic G, Andrić D, Roglić G, Kostić-Rajačić S. Two new phenylpiperazines with atypical antipsychotic potential. in Bioorganic and Medicinal Chemistry Letters. 2007;17(21):5749-5753.
doi:10.1016/j.bmcl.2007.08.066 .

Tomic, Mirko, Ignjatović, Đurđica, Tovijovic, Gordana, Andrić, Deana, Roglić, Goran, Kostić-Rajačić, Slađana, "Two new phenylpiperazines with atypical antipsychotic potential" in Bioorganic and Medicinal Chemistry Letters, 17, no. 21 (2007):5749-5753,
https://doi.org/10.1016/j.bmcl.2007.08.066 . .

TY  - JOUR
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Andrić, Deana
AU  - Kostić-Rajačić, Slađana
AU  - Šoškić, Vukić
AU  - Roglić, Goran
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/876
AB  - Clinical properties of atypical antipsychotics are based on their interaction with D-2 dopamine receptor and serotonin 5-HT1A and 5-HT2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1-cinnamyl-4-(2-methoxyphenyl)piperazines, and evaluated their affinities for D2, 5-HT1A, 5-HT2A, and adrenergic (a,) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the alpha(1) receptor. Docking analysis indicated that the binding to D2 and 5-HT1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge-to-face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv der Pharmazie
T1  - 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors
VL  - 340
IS  - 9
SP  - 456
EP  - 465
DO  - 10.1002/ardp.200700062
ER  - 

@article{
author = "Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Kostić-Rajačić, Slađana and Šoškić, Vukić and Roglić, Goran",
year = "2007",
abstract = "Clinical properties of atypical antipsychotics are based on their interaction with D-2 dopamine receptor and serotonin 5-HT1A and 5-HT2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1-cinnamyl-4-(2-methoxyphenyl)piperazines, and evaluated their affinities for D2, 5-HT1A, 5-HT2A, and adrenergic (a,) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the alpha(1) receptor. Docking analysis indicated that the binding to D2 and 5-HT1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge-to-face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv der Pharmazie",
title = "1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors",
volume = "340",
number = "9",
pages = "456-465",
doi = "10.1002/ardp.200700062"
}

Penjišević, J., Šukalović, V., Andrić, D., Kostić-Rajačić, S., Šoškić, V.,& Roglić, G.. (2007). 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors. in Archiv der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 340(9), 456-465.
https://doi.org/10.1002/ardp.200700062

Penjišević J, Šukalović V, Andrić D, Kostić-Rajačić S, Šoškić V, Roglić G. 1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors. in Archiv der Pharmazie. 2007;340(9):456-465.
doi:10.1002/ardp.200700062 .

Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Kostić-Rajačić, Slađana, Šoškić, Vukić, Roglić, Goran, "1-cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D-2) and serotonin (5-HT1A) receptors" in Archiv der Pharmazie, 340, no. 9 (2007):456-465,
https://doi.org/10.1002/ardp.200700062 . .

TY  - JOUR
AU  - Andrić, Deana
AU  - Tovilović, Gordana
AU  - Roglić, Goran
AU  - Vasković, Đurđica
AU  - Šoškić, Vukić
AU  - Tomic, Mirko
AU  - Kostić-Rajačić, Slađana
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/845
AB  - Six newly synthesized heterocyclic (2-nitroplienyl)piperazines. with a specific structure of the heteroaryl group, which mimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and alpha I receptors. All compounds with a benzimidazole group had a 5-HT2A/D-2 receptors binding ratio characteristic for atypical neuroleptics ( gt  1, pK(i) values). Compound 7e, 4-bromo-6-{2-[4-(2-nitrophenyl)piperazin-1-yl]etliyl}-1H-benziniidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations.
AB  - Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike ( gt 1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Synthesis and pharmacological evaluation of several N-(2-nitrophenyl)piperazine derivatives
T1  - Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina
VL  - 72
IS  - 5
SP  - 429
EP  - 435
DO  - 10.2298/JSC0705429A
ER  - 

@article{
author = "Andrić, Deana and Tovilović, Gordana and Roglić, Goran and Vasković, Đurđica and Šoškić, Vukić and Tomic, Mirko and Kostić-Rajačić, Slađana",
year = "2007",
abstract = "Six newly synthesized heterocyclic (2-nitroplienyl)piperazines. with a specific structure of the heteroaryl group, which mimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles), were evaluated for their binding affinity to rat dopamine (DA), serotonin (5-HT) and alpha I receptors. All compounds with a benzimidazole group had a 5-HT2A/D-2 receptors binding ratio characteristic for atypical neuroleptics ( gt  1, pK(i) values). Compound 7e, 4-bromo-6-{2-[4-(2-nitrophenyl)piperazin-1-yl]etliyl}-1H-benziniidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations., Sintetisano je šest heterocikličnih (2-nitrofenil)piperazina sa specifičnom heteroaril grupom, koja podražava kateholsku grupu dopamina (benzimidazoli i supstituisani benzimidazoli), i ispitan je njihov afinitet ka dopaminskim, serotoninskim i _1 receptorima. Sva jedinjenja sa benzimidazolskim grupama su pokazala 5-HT 1A/D2 odnos vezivanja karakterističan za atipične neuroleptike ( gt 1, pK i vrednosti). Jedinjenje 7c, 4-bromo-6-{2-_4-(2-nitrofenil)piperazin-1-il_etil}-1H-benzimidazol, pokazalo je izraženiji afinitet ka svim klasama receptora u poređenju sa klozapinom i takođe predstavlja jedinjenje sa najboljim karakteristikama za dalja in vivo istraživanja.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Synthesis and pharmacological evaluation of several N-(2-nitrophenyl)piperazine derivatives, Sinteza i farmakološko ispitivanje novih derivata N-(2-nitrofenil) piperazina",
volume = "72",
number = "5",
pages = "429-435",
doi = "10.2298/JSC0705429A"
}

Andrić, D., Tovilović, G., Roglić, G., Vasković, Đ., Šoškić, V., Tomic, M.,& Kostić-Rajačić, S.. (2007). Synthesis and pharmacological evaluation of several N-(2-nitrophenyl)piperazine derivatives. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 72(5), 429-435.
https://doi.org/10.2298/JSC0705429A

Andrić D, Tovilović G, Roglić G, Vasković Đ, Šoškić V, Tomic M, Kostić-Rajačić S. Synthesis and pharmacological evaluation of several N-(2-nitrophenyl)piperazine derivatives. in Journal of the Serbian Chemical Society. 2007;72(5):429-435.
doi:10.2298/JSC0705429A .

Andrić, Deana, Tovilović, Gordana, Roglić, Goran, Vasković, Đurđica, Šoškić, Vukić, Tomic, Mirko, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of several N-(2-nitrophenyl)piperazine derivatives" in Journal of the Serbian Chemical Society, 72, no. 5 (2007):429-435,
https://doi.org/10.2298/JSC0705429A . .

TY  - JOUR
AU  - Zlatović, Mario
AU  - Šukalović, Vladimir
AU  - Kostić-Rajačić, Slađana
AU  - Andrić, Deana
AU  - Roglić, Goran
PY  - 2006
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/818
AB  - Scrotonin receptors (5-HTRs), especially the 5-HT1A subtype, have been the subject of intensive research for the past decade, due to their function in human physiology. Several structurally different classes of ligands are known to bind to the 5-HT1A receptor, but arylpiperazine derivatives are among the most important ligands. In the work, docking analyses were used to explain the binding affinities of a series of ligands with different N-1 substituent. All ligands had ill common the arylpiperazine structure, while the N-1 substituent was modified to investigate the influence of ligand structure on its binding affinity. The shape and size, as well as the rigidity of the substituents were altered to investigate the possible effects on the formation of the receptor - ligand complex.
AB  - Serotoninski receptori su, a naročito 5-HT 1A pod tip, zbog značajne uloge u fiziologiji ljudskog organizma, predmet intenzivnog izučavanja tokom protekle decenije. Poznato je da se za 5-HT 1A receptor vezuje nekoliko strukturno različitih klasa liganada, ali su arilpiperazinski derivati među najznačajnijim. Da bi objasnili vezivanje serije liganada sa različitim N-1 supstituentima za receptor koristili smo analizu vezivanja (docking analizu). Svi ligandi su imali zajedničku arilpiperazinsku strukturu dok su im N-1 supstituenti modifikovani tako što je menjan oblik, veličina kao i krutost supstituenta da bi se istražio njihov eventualni uticaj na formiranje kompleksa receptor - ligand.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor
T1  - Uticaj osobina N-1 supstituenta na afinitet arilpiperazina prema vezivnom mestu 5-HT1A receptora
VL  - 71
IS  - 11
SP  - 1125
EP  - 1135
DO  - 10.2298/JSC0611125Z
ER  - 

@article{
author = "Zlatović, Mario and Šukalović, Vladimir and Kostić-Rajačić, Slađana and Andrić, Deana and Roglić, Goran",
year = "2006",
abstract = "Scrotonin receptors (5-HTRs), especially the 5-HT1A subtype, have been the subject of intensive research for the past decade, due to their function in human physiology. Several structurally different classes of ligands are known to bind to the 5-HT1A receptor, but arylpiperazine derivatives are among the most important ligands. In the work, docking analyses were used to explain the binding affinities of a series of ligands with different N-1 substituent. All ligands had ill common the arylpiperazine structure, while the N-1 substituent was modified to investigate the influence of ligand structure on its binding affinity. The shape and size, as well as the rigidity of the substituents were altered to investigate the possible effects on the formation of the receptor - ligand complex., Serotoninski receptori su, a naročito 5-HT 1A pod tip, zbog značajne uloge u fiziologiji ljudskog organizma, predmet intenzivnog izučavanja tokom protekle decenije. Poznato je da se za 5-HT 1A receptor vezuje nekoliko strukturno različitih klasa liganada, ali su arilpiperazinski derivati među najznačajnijim. Da bi objasnili vezivanje serije liganada sa različitim N-1 supstituentima za receptor koristili smo analizu vezivanja (docking analizu). Svi ligandi su imali zajedničku arilpiperazinsku strukturu dok su im N-1 supstituenti modifikovani tako što je menjan oblik, veličina kao i krutost supstituenta da bi se istražio njihov eventualni uticaj na formiranje kompleksa receptor - ligand.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor, Uticaj osobina N-1 supstituenta na afinitet arilpiperazina prema vezivnom mestu 5-HT1A receptora",
volume = "71",
number = "11",
pages = "1125-1135",
doi = "10.2298/JSC0611125Z"
}

Zlatović, M., Šukalović, V., Kostić-Rajačić, S., Andrić, D.,& Roglić, G.. (2006). Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 71(11), 1125-1135.
https://doi.org/10.2298/JSC0611125Z

Zlatović M, Šukalović V, Kostić-Rajačić S, Andrić D, Roglić G. Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor. in Journal of the Serbian Chemical Society. 2006;71(11):1125-1135.
doi:10.2298/JSC0611125Z .

Zlatović, Mario, Šukalović, Vladimir, Kostić-Rajačić, Slađana, Andrić, Deana, Roglić, Goran, "Influence of N-1 substituent properties on binding affinities of arylpiperazines to the binding site of 5-HT1A receptor" in Journal of the Serbian Chemical Society, 71, no. 11 (2006):1125-1135,
https://doi.org/10.2298/JSC0611125Z . .