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
Authorized Users Only
Article (Published version)
MetadataShow full item record
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.
Keywords:Dopamine receptor / Rational drug design / Serotonin receptor
Source:European Journal of Medicinal Chemistry, 2008, 43, 8, 1696-1705
- Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux