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.
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-(omega-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.
Soni
Love Kumar
LK
Molecular Modelling Study Group, CADD Laboratory, Computational Chemistry Research, Department of Pharmacy, Shri G.S. Institute of Technology and Science, Indore 452 003, India. lovesoni@hotmail.com
Kaskhedikar
Satish Gopalrao
SG
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D053778:Thiazolidines; D000449:Aldehyde Reductase