DOCKING AND PHYSICOCHEMICAL SIMILARITY STUDIES ON INDOLE BASED ATYPICAL ANTIPSYCHOTICS

Alka Bali* and Umesh Sen

A hypothetical binding model has been proposed based on in silico (docking studies) on a series of indole derivatives with atypical antipsychotic activity in order to investigate their hypothetical binding mode with respect to the dopaminergic D3 receptors. The docking reproduced the established receptor binding profile of the standard drugs ziprasidone, risperidone, ketanserin, clozapine and eticlopride. The test compounds demonstrated a similar binding profile to the standard drugs. Salient interactions noted for the standard drugs as well as the test compounds were the hydrogen bonding interactions with the residues Asp110, Tyr373, Ser182, Ser192, Cys181 and π-π stacking with Phe345, Phe346 and His349. The D₃ docking scores of the compounds lacking the atypical profile were seen to be lower compared to those having an atypical profile. Further, the physicochemical similarity of the test compounds was assessed with respect to selected standard drugs and the test compounds were seen to possess very good similarity to ziprasidone.