Interaction of arylpiperazines with the dopamine receptor D-2 binding site
Autori
Šukalović, VladimirZlatović, Mario
Andrić, Deana
Roglić, Goran
Kostić-Rajačić, Slađana
Šoškić, Vukić
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The docking of several 1-benzyl-4-arylpiperazines to the dopamine receptor (DAR) D-2 was examined. The results demonstrated that the interaction of protonated NI of the piperazine ring with Asp 86 (III.32) and edge-to-face interactions of the aromatic ring of the arylpiperazine part of the ligand with Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) of the receptor, represent the major stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could build one more hydrogen bond with Trp 182 (VI.48). Bulky substituents; in position 4 were not tolerated due to the unfavorable sterical interaction with Phe 178 (VI.44). Substituents in position 2 and 3 were found to be sterically well tolerated. Introduction of electron attractive -NO2 group in position 3 of arylpiperazines decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity comparing to that of the phenylpiperazine 1. Thi...s can be explained in terms of favoured edge-to-face interactions in ligands with a high negative electrostatic surface potential (ESP) in the centre of aromatic residue of arylpiperazines. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands to form complexes with the DAR D-2. Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) can be considered as a part of the ancillary DAR D-2 pocket preserved in most G protein-coupled receptors of the A class and obviously, the arylpiperazine structural motif represents one of the privileged structures that bind to this pocket.
Ključne reči:
arylpiperazines, binding pocket, D-2 receptor, interaction / modelling / dopamine D-2 agonistsIzvor:
Arzneimittel-forschung = Drug Research, 2005, 55, 3, 145-152Izdavač:
- Ecv-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Šukalović, Vladimir AU - Zlatović, Mario AU - Andrić, Deana AU - Roglić, Goran AU - Kostić-Rajačić, Slađana AU - Šoškić, Vukić PY - 2005 UR - https://cherry.chem.bg.ac.rs/handle/123456789/690 AB - The docking of several 1-benzyl-4-arylpiperazines to the dopamine receptor (DAR) D-2 was examined. The results demonstrated that the interaction of protonated NI of the piperazine ring with Asp 86 (III.32) and edge-to-face interactions of the aromatic ring of the arylpiperazine part of the ligand with Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) of the receptor, represent the major stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could build one more hydrogen bond with Trp 182 (VI.48). Bulky substituents; in position 4 were not tolerated due to the unfavorable sterical interaction with Phe 178 (VI.44). Substituents in position 2 and 3 were found to be sterically well tolerated. Introduction of electron attractive -NO2 group in position 3 of arylpiperazines decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity comparing to that of the phenylpiperazine 1. This can be explained in terms of favoured edge-to-face interactions in ligands with a high negative electrostatic surface potential (ESP) in the centre of aromatic residue of arylpiperazines. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands to form complexes with the DAR D-2. Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) can be considered as a part of the ancillary DAR D-2 pocket preserved in most G protein-coupled receptors of the A class and obviously, the arylpiperazine structural motif represents one of the privileged structures that bind to this pocket. PB - Ecv-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf T2 - Arzneimittel-forschung = Drug Research T1 - Interaction of arylpiperazines with the dopamine receptor D-2 binding site VL - 55 IS - 3 SP - 145 EP - 152 UR - https://hdl.handle.net/21.15107/rcub_cherry_690 ER -
@article{ author = "Šukalović, Vladimir and Zlatović, Mario and Andrić, Deana and Roglić, Goran and Kostić-Rajačić, Slađana and Šoškić, Vukić", year = "2005", abstract = "The docking of several 1-benzyl-4-arylpiperazines to the dopamine receptor (DAR) D-2 was examined. The results demonstrated that the interaction of protonated NI of the piperazine ring with Asp 86 (III.32) and edge-to-face interactions of the aromatic ring of the arylpiperazine part of the ligand with Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) of the receptor, represent the major stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could build one more hydrogen bond with Trp 182 (VI.48). Bulky substituents; in position 4 were not tolerated due to the unfavorable sterical interaction with Phe 178 (VI.44). Substituents in position 2 and 3 were found to be sterically well tolerated. Introduction of electron attractive -NO2 group in position 3 of arylpiperazines decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity comparing to that of the phenylpiperazine 1. This can be explained in terms of favoured edge-to-face interactions in ligands with a high negative electrostatic surface potential (ESP) in the centre of aromatic residue of arylpiperazines. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands to form complexes with the DAR D-2. Phe 178 (VI.44), Trp 182 (VI.48) and Tyr 216 (VII.58) can be considered as a part of the ancillary DAR D-2 pocket preserved in most G protein-coupled receptors of the A class and obviously, the arylpiperazine structural motif represents one of the privileged structures that bind to this pocket.", publisher = "Ecv-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf", journal = "Arzneimittel-forschung = Drug Research", title = "Interaction of arylpiperazines with the dopamine receptor D-2 binding site", volume = "55", number = "3", pages = "145-152", url = "https://hdl.handle.net/21.15107/rcub_cherry_690" }
Šukalović, V., Zlatović, M., Andrić, D., Roglić, G., Kostić-Rajačić, S.,& Šoškić, V.. (2005). Interaction of arylpiperazines with the dopamine receptor D-2 binding site. in Arzneimittel-forschung = Drug Research Ecv-Editio Cantor Verlag Medizin Naturwissenschaften, Aulendorf., 55(3), 145-152. https://hdl.handle.net/21.15107/rcub_cherry_690
Šukalović V, Zlatović M, Andrić D, Roglić G, Kostić-Rajačić S, Šoškić V. Interaction of arylpiperazines with the dopamine receptor D-2 binding site. in Arzneimittel-forschung = Drug Research. 2005;55(3):145-152. https://hdl.handle.net/21.15107/rcub_cherry_690 .
Šukalović, Vladimir, Zlatović, Mario, Andrić, Deana, Roglić, Goran, Kostić-Rajačić, Slađana, Šoškić, Vukić, "Interaction of arylpiperazines with the dopamine receptor D-2 binding site" in Arzneimittel-forschung = Drug Research, 55, no. 3 (2005):145-152, https://hdl.handle.net/21.15107/rcub_cherry_690 .