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.
Soni
Love Kumar
LK
CADD Laboratory, Department of Pharmacy, Shri G. S. Institute of Technology & Science, Indore, India. lovesoni@hotmail.com
Kaskhedikar
Satish G
SG
D000085:Acetates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008961:Models, Structural; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000085:Acetates; D004791:Enzyme Inhibitors; D013844:Thiazoles; D000449:Aldehyde Reductase