Exploring structural requirements for aldose-reductase inhibition by 2,4-dioxo-5-(naphth-2-ylmethylene)-3-thiazolidinyl acetic acids and 2-thioxo analogues: Fujita-Ban and Hansch approach.

A Quantitative Structure-Activity Relationship (QSAR) study based on Fujita-Ban and classical Hansch approach was performed on 2,4-dioxo-5-(naphth-2-ylmethylene)-3-thiazolidinyl acetic acids and 2-thioxo analogues to gain structural insight into the binding mode of the molecules to the aldose-reductase enzyme. First, the Fujita-Ban approach has been followed, which revealed the highest activity contribution for 2-thioxo analogues of 3-thiazolidinyl acetic acids as compared to 2,4-dioxo analogues. Further, the Hansch approach confirms that 2-thioxo-4-oxo-3-thiazolidinyl acetic acids are conducive to aldose-reductase inhibitory activity. The hydrophobic properties of the various substituents have been found to play major roles in the binding of these compounds with the receptor.