Novel thiazolidinedione (TZD) scaffolds as aldose reductase inhibitors, synthesis and molecular docking studies

Abstract

A series of Thiazolidinedione (TZD) scaffold libraries 6(a-o) and 7(a-o) were synthesized and confirmed their structures by interpretation of FTIR, 1H NMR, 13C NMR and Mass spectroscopic investigations. They were screened for the inhibitory activity against aldose reductase enzyme. The intermediates 6(a-o) with ester moiety series showed potent antidiabetic activity. Further, conversion of ester 6(a-o) into acids 7(a-o) showed additional increase in the antidiabetic activity ranging from 0.24 ± 0.34 to 2.38 ± 0.76 µM with respect to the standard drug Sorbinil 2.01 ± 0.25 µM. The molecular docking studies performed against the crystal structure of aldose reductase (PDB ID: 1PWM) well defined the binding interactions compounds with notable docking scores, in which compounds 6g, 6h and 7h showed good hydrogen bonding interactions and 7h showed highest docking score.