Synthesis and biological evaluation of novel isatin-hydrazide conjugates as potential antidiabetic agents

Abstract

Diabetes mellitus is a severe metabolic disorder, which has very high prevalence rate and resulting into other health devastating complications. Pancreatic insulin resistance and -cell dysfunction are its defining features resulting in high blood glucose level. This study's objective was to locate substances with possible anti-hyperglycemic effect that block α-glucosidase. For these studies several novel indole-hydrazide conjugates (3a–3r) were synthesized and examined using a variety of spectroscopic methods. Comparing the investigated compounds from the 3a–3r series to the reference medication acarbose 1C50 = 873.34 ± 1.67 µM, all the compounds demonstrated potent inhibition of α-glucosidase with IC50 values of in range of 0.51–42.91 µM. The highest inhibition was seen with the analogs 3p and 3o having IC50 values of 0.51 ± 0.06 and 1.57 ± 0.08 µM, respectively. Structure-activity relationships showed that the α-glucosidase potential of these compounds vary with various substituents pattern on the novel indole-hydrazide. Kinetics and docking examination revealed that the active compounds accommodate well in the active site of α-glucosidase and displayed mixed-type of inhibition.