Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor

Authors

DOI:

https://doi.org/10.2298/JSC181029104P

Keywords:

arylpiperazines, molecular dynamics, molecular docking, receptor binding site

Abstract

A total of 14 novel arylpiperazines were synthesized, and pharmacologically
evaluated by measuring their affinities towards the D2 dopamine receptor
(DRD2) in a [3H]spiperone competition assay. All the herein described compounds
consist of a benzimidazole moiety connected to N-(2-methoxyphenyl)piperazine
via linkers of various lengths. Molecular docking analysis and molecular dynamics
simulations were performed on the DRD2–arylpiperazine complexes with the
objective of exploring the receptor–ligand interactions and properties of the receptor
binding site. The recently published crystal structure of DRD2 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
DRD2 and therefore should contain a linker of 5 or 6 methylene groups long.

Author Biographies

Jelena Z. Penjišević, ICTM-Department of Chemistry, University of Belgrade, Njegoševa 12, 11000 Belgrade

Assistant Research Professor,

Department of Chemistry

Deana B. Andrić, Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade

Associate professor,

Department of Organic Chemistry


Vladimir B. Šukalović, ICTM-Department of Chemistry, University of Belgrade, Njegoševa 12, 11000 Belgrade

Assistant Research Professor,

Department of Chemistry

 

Goran M. Roglić, Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade

Full professor

Department of Applied Chemistry

Vukić Šoškić, Orgentec GmbH, Carl-Zeiss-Str. 49, 55129 Mainz

Full Professor

Slađana Kostić-Rajačić, ICTM-Department of Chemistry, University of Belgrade, Njegoševa 12, 11000 Belgrade

Full Research Professor,Department of Chemistry

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Published

2019-10-06

How to Cite

[1]
J. Z. Penjišević, D. B. Andrić, V. B. Šukalović, G. M. Roglić, V. Šoškić, and S. Kostić-Rajačić, “Synthesis of novel 2-(piperazino-1-yl-alkyl)-1H-benzimidazole derivates and assessment of their interactions with the D2 dopamine receptor”, J. Serb. Chem. Soc., vol. 84, no. 9, pp. 925-934, Oct. 2019.

Issue

Section

Organic Chemistry

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