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

Abstract

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.

Exploration of QSAR modelling techniques and their combination to rationalize the physicochemical characters of nitrophenyl derivatives towards aldose reductase inhibition

“…Due to the shortage of drugs currently available for the treatment of diabetic complications, the search for new ARIs endowed with more favourable biological properties is still a major pharmaceutical challenge. In our recent publications [12][13][14] and many other researchers [15][16][17] have reported the QSAR analysis of different aldose reductase inhibitors. To gain insight into the structural and molecular requirements influencing the aldose reductase inhibitor activity, we herein describe QSAR analysis of nirophenyl derivatives.…”

QSAR study of 5-arylidene-2,4-thiazolidinediones as aldose reductase inhibitors

“…Moreover, from the pioneering studies on sorbinil and alrestatin to recent investigation on zopolrestat and zenarestat, several compounds in clinical trials or on the market for the treatment of the diabetic complications have been developed but were subsequently withdrawn, suggesting that no universally potent inhibitor currently exists. This demands the development of potent inhibitors (Costantino et al, 1999;Miyamoto, 2002;Soni and Kaskhedikar, 2006;Amic et al, 1997;Stefanic-Petek et al, 2002;Prabhakar et al, 2006). To gain insight into the structural and molecular requirements influencing the aldose reductase inhibitor activity, we herein describe QSAR analysis of 5-arylidene-2,4-thiazolidinediones (Maccari et al, 2005).…”

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

“…In our recent publication, 22) we have reported the QSAR analysis of 2,4-dioxo-5-(naphthylmethylene)-3-thiazolidineaceticacids and 2-thioxo analogues as aldose reductase inhibitors. Owing to our special interest in thiazolidine derivatives for the management of diabetes mellitus and in continuation with our previous work, we attempted to rationalize the title compound in terms of physicochemical and structural requirements.…”