Synthesis of novel piperazino-alkyl-1H-benzo[d]imidazole derivates and assessment of their interactions with the D2 dopamine receptor

Jelena Z. Penjiševic, Deana B. Andrić, Vladimir B. Šukalović, Goran M. Roglić, Vukić Šoškić, Slađana Kostić-Rajačić

Abstract


A total of 14 novel arylpiperazines were synthesized, and pharmaco­logic­ally evaluated by measuring their affinities towards the D2 dopamine receptor (D2DR) in a [3H]spiperone competition assay. All herein described compounds consist of a benzimidazole moiety connected to the N-(2-methoxyphenyl)pipe­razine via linkers of various lengths. Molecular docking analysis and molecular dynamics simulations were performed on D2DR-arylpiperazine complexes with an objective to explore the receptor-ligand interactions and properties of the receptor binding site. Crystal structure of D2DR that has been published recently 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 D2DR and therefore should contain a linker of 5 or 6 methylene groups long.


Keywords


arylpiperazines; molecular dynamics; molecular docking; receptor bind site

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DOI: https://doi.org/10.2298/JSC181029104P

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