Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines
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2004
Authors
Šukalović, VladimirZlatović, Mario
Andrić, Deana
Roglić, Goran
Kostić-Rajačić, Slađana
Šoškić, Vukić
Article (Published version)
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Docking of several 1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}-4- and 1-benzylarylpiperazines to the D-2 dopamine receptor (DAR) was examined. The binding pocket of the D-2 DAR defined according to Teeter and DuRand [1] was extended using the Insight II software. It was found that (i) the interaction of the protonated N1 of the piperazine ring with Asp86, (ii) the hydrogen bond formation between the benzimidazole part of the ligand and Ser141, as well as Ser122, and (iii) the edge-to-face interactions of the aromatic ring or arylpiperazine part of the ligand with Phe178, Tyr216 and Trpl 82 of the receptor represent the mayor stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could form one more hydrogen bond with Trp182. Bulky substituents in position 4 are not tolerated, due to the unfavorable sterical interaction with Phe178. Substituents in positions 2 and 3 are sterically well tolerated. Electron-attractive groups (F, Cl..., CF3, and NO2) decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity, as compared to that of the parent compound 1. This can be explained by strong edge-to-face interactions of negative electrostatic surface potential (ESP) in the center of aromatic residues of the ligand with positive-ESP protons in the aromatic residues of the receptor. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands forming complexes with the D-2 DAR.
Keywords:
arylpiperazines / D-2 receptor / modeling / interaction / binding pocketSource:
Archiv der Pharmazie, 2004, 337, 9, 502-512Publisher:
- Wiley-V C H Verlag Gmbh, Weinheim
DOI: 10.1002/ardp.200400901
ISSN: 0365-6233
PubMed: 15362123
WoS: 000224140000005
Scopus: 2-s2.0-4644326189
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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 - 2004 UR - https://cherry.chem.bg.ac.rs/handle/123456789/663 AB - Docking of several 1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}-4- and 1-benzylarylpiperazines to the D-2 dopamine receptor (DAR) was examined. The binding pocket of the D-2 DAR defined according to Teeter and DuRand [1] was extended using the Insight II software. It was found that (i) the interaction of the protonated N1 of the piperazine ring with Asp86, (ii) the hydrogen bond formation between the benzimidazole part of the ligand and Ser141, as well as Ser122, and (iii) the edge-to-face interactions of the aromatic ring or arylpiperazine part of the ligand with Phe178, Tyr216 and Trpl 82 of the receptor represent the mayor stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could form one more hydrogen bond with Trp182. Bulky substituents in position 4 are not tolerated, due to the unfavorable sterical interaction with Phe178. Substituents in positions 2 and 3 are sterically well tolerated. Electron-attractive groups (F, Cl, CF3, and NO2) decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity, as compared to that of the parent compound 1. This can be explained by strong edge-to-face interactions of negative electrostatic surface potential (ESP) in the center of aromatic residues of the ligand with positive-ESP protons in the aromatic residues of the receptor. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands forming complexes with the D-2 DAR. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - Archiv der Pharmazie T1 - Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines VL - 337 IS - 9 SP - 502 EP - 512 DO - 10.1002/ardp.200400901 ER -
@article{ author = "Šukalović, Vladimir and Zlatović, Mario and Andrić, Deana and Roglić, Goran and Kostić-Rajačić, Slađana and Šoškić, Vukić", year = "2004", abstract = "Docking of several 1-{2-[5-(1H-benzimidazole-2-thione)]ethyl}-4- and 1-benzylarylpiperazines to the D-2 dopamine receptor (DAR) was examined. The binding pocket of the D-2 DAR defined according to Teeter and DuRand [1] was extended using the Insight II software. It was found that (i) the interaction of the protonated N1 of the piperazine ring with Asp86, (ii) the hydrogen bond formation between the benzimidazole part of the ligand and Ser141, as well as Ser122, and (iii) the edge-to-face interactions of the aromatic ring or arylpiperazine part of the ligand with Phe178, Tyr216 and Trpl 82 of the receptor represent the mayor stabilizing forces. Besides, the hydrogen bond acceptor group in position 2 of the phenylpiperazine aromatic ring could form one more hydrogen bond with Trp182. Bulky substituents in position 4 are not tolerated, due to the unfavorable sterical interaction with Phe178. Substituents in positions 2 and 3 are sterically well tolerated. Electron-attractive groups (F, Cl, CF3, and NO2) decreased, while electron donors (-OMe) and the second aromatic ring (naphthyl) increased the binding affinity, as compared to that of the parent compound 1. This can be explained by strong edge-to-face interactions of negative electrostatic surface potential (ESP) in the center of aromatic residues of the ligand with positive-ESP protons in the aromatic residues of the receptor. Thus, besides the salt bridges and hydrogen bonds, edge-to-face interactions significantly contribute to arylpiperazine ligands forming complexes with the D-2 DAR.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "Archiv der Pharmazie", title = "Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines", volume = "337", number = "9", pages = "502-512", doi = "10.1002/ardp.200400901" }
Šukalović, V., Zlatović, M., Andrić, D., Roglić, G., Kostić-Rajačić, S.,& Šoškić, V.. (2004). Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines. in Archiv der Pharmazie Wiley-V C H Verlag Gmbh, Weinheim., 337(9), 502-512. https://doi.org/10.1002/ardp.200400901
Šukalović V, Zlatović M, Andrić D, Roglić G, Kostić-Rajačić S, Šoškić V. Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines. in Archiv der Pharmazie. 2004;337(9):502-512. doi:10.1002/ardp.200400901 .
Šukalović, Vladimir, Zlatović, Mario, Andrić, Deana, Roglić, Goran, Kostić-Rajačić, Slađana, Šoškić, Vukić, "Modeling of the D-2 dopamine receptor arylpiperazine binding site for 1-{2-[5-(1H-benzimidazoIe-2-thione)]ethyl}-4-arylpiperazines" in Archiv der Pharmazie, 337, no. 9 (2004):502-512, https://doi.org/10.1002/ardp.200400901 . .