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

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 alpha-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 mu M, all the compounds demonstrated potent inhibition of alpha-glucosidase with IC50 values of in range of 0.51-42.91 mu M. The highest inhibition was seen with the analogs 3p and 3o having IC50 values of 0.51 +/- 0.06 and 1.57 +/- 0.08 mu M, respectively. Structure-activity relationships showed that the alpha-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 alpha-glucosidase and displayed mixed-type of inhibition.