Structure-Based Virtual Screening for Differential Inhibition of Aldose Reductase, Implicated in Secondary Complications in Diabetes

Abstract

As a clinically relevant drug target, there have been several attempts to design a structure-based inhibitor for aldose reductase (AR). Since most of the aldehydes are presented to AR conjugated with glutathione, in present work, the structure of AR complexed with NADPH and a glutathione analog was used as a target for virtual screening of small molecule library. Due to interactions of the glutathione backbone with the binding pocket of AR, the ternary complex (AR●NADPH●DCEG) represents a unique conformation of AR backbone. NCI diversity set V was used as a small molecules library for virtual screening. AutoDock Vina was used for docking and scoring of ligands. Few select hits with low binding free energy were obtained, which may be potential leads for a search of an differential inhibitor against AR.