title: 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.
abstract: 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 D(1)-like and D(2)-like, and serotonin 5-HT(1A) receptors was evaluated using the radioligand binding assays. All compounds tested had affinity for the D(2)-like and 5-HT(1A) receptors, but were inactive towards the D(1)-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 D(2)-like and Trp-358 of the 5-HT(1A) receptor. Energy contributions for these interactions were calculated using the ab initio method.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia.
authors.forename: Deana
authors.initials: D
authors.lastname: Andrić
authors.forename: Goran
authors.initials: G
authors.lastname: Roglić
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sukalović
authors.forename: Vukić
authors.initials: V
authors.lastname: Soskić
authors.forename: Sladjana
authors.initials: S
authors.lastname: Kostić-Rajacić
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D006219:Halogens / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D006219:Halogens; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D044263:Receptors, Serotonin, 5-HT1; D000077489:Piperazine; C031000:benzimidazole