Hybrids of Isatin-Pyrazole as Potential alpha-Glucosidase Inhibitors: Synthesis, Biological Evaluations and Molecular Docking Studies

alpha-Glucosidase inhibition has been considered as an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. A series of novel isatin-pyrazole hybrids has been rationally designed, synthesized and characterized by different spectroscopic techniques. All of the synthesized compounds were evaluated for their alpha-glucosidase inhibitory potential using in vitro enzymatic assay. The tested compounds have exhibited potent alpha-glucosidase inhibition with IC50 values ranging from 3.26 +/- 0.25 to 32.33 +/- 1.08 mu M. Compound V7, having 3-nitro phenyl ring appended at pyrazole nucleus, has emerged as the most potent inhibitor among the series with an IC50 value of 3.26 +/- 0.25 mu M, which was approximately 146 fold more potent than the clinically used drug acarbose (IC50 = 478.07 +/- 1.53 mu M). Molecular docking studies were carried out to investigate the binding interactions of most active compounds with the active site of the enzyme. Further, in silico predictive pharmacokinetic parameters (ADME) and drug-like properties of the compounds were within the acceptable ranges. In vivo biological evaluations further supplemented the in vitro results.