Exploring Structural Feature of Aldose-Reductase Inhibition by 5-[[2-(ω-Carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine Derivatives Employing Fujita–Ban and Hansch Approach

Abstract

Designing of a highly selective, potent and safe inhibitor of aldose reductase (ALR) capable of potentially blocking the excess glucose flux through the polyol pathway that prevails under diabetic condition has been a long standing challenge. In our study, we did quantitative structure–activity relationship (QSAR) analysis, based on Fujita–Ban and classical Hansch approach, on 5-[[2-(ω-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives. Study gave structural insight into the binding mode of the molecules to the aldose reductase enzyme. The Fujita–Ban approach revealed that benzylidene thiazolidine nucleus is more potent as compare to naphthyl-methylene thiazolidine analogs. The bulkierness of naphthyl-methylene might be inquisitive with receptor. Hansch approach suggested that electron-withdrawing groups are conducive to aldose reductase inhibitory activity.