Synthesis and biological evaluation of isatin derivatives containing 1,3,4-thiadiazole as potent a-glucosidase inhibitors.

ABSTRACT

A series of (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-substituted indolin-2-ones derivatives (3a-3m) were designed and synthesized. All newly synthesized compounds were evaluated for their a-glucosidase inhibitory activity with resveratrol as positive control in vitro. Except for 3i and 3j, all of the compounds showed a potent inhibitory activity against a-glucosidase with IC50 values in the range of 3.12 ± 1.25 to 45.95 ± 1.26 µM and the purity of these compounds was greater than 95%. The IC50 values were being compared to the standard resveratrol (IC50 = 22.00 ± 1.15 µM) and it was found that compounds 3b, 3d-3h were found to be more active than resveratrol. Specifically, (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-(4-chlorobenzyl)indolin-2-one (3d) exhibited the most potent a-glucosidase inhibitory activity with IC50 value of 3.12 ± 1.25 µM. The kinetic analysis revealed that compound (3d) is noncompetitive inhibitor. Structure activity relationship has been established for all compounds. Furthermore, the binding interactions of compound 3d with the active site of a-glucosidase were confirmed through molecular docking. This study has identified a new class of potent a-glucosidase inhibitors for further investigation.