Synthesis, binding properties and receptor docking of 4-halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles, mixed ligands of D2 and 5-HT1A receptors

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 D1-like and D2-like, and serotonin 5-HT1A receptors was evaluated using the radioligand binding assays. All compounds tested had affinity for the D2-like and 5-HT1A receptors, but were inactive towards the D1-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 D2-like and Trp-358 of the 5-HT1A receptor. Energy contributions for these interactions were calculated using the ab initio method.

Graphical abstract4-Halo-6-[2-(4-arylpiperazin-1-yl)ethyl]-1H-benzimidazoles tested in this study have moderate to high affinity for serotonin 5-HT1A and D2-like dopamine receptors. In silico docking analysis of selected ligands was performed in order to explain obtained results. Figure optionsDownload full-size imageDownload as PowerPoint slide