Discovery of imidazopyridine derived oxadiazole-based thiourea derivatives as potential anti-diabetic agents: Synthesis, in vitro antioxidant screening and in silico molecular modeling approaches

A series of new imidazopyridine based oxadiazole derivatives (5a-l) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including & alpha;-glucosidase, & alpha;-amylase inhibitory, and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2 & PRIME;-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. The inhibitory activity results revealed that all the synthesized analogs displayed significant & alpha;-glucosidase and & alpha;-amylase inhibition with IC50 values of 0.90 & PLUSMN; 0.10 to 18.10 & PLUSMN; 0.20 & mu;M (for & alpha;-glucosidase) and 1.10 & PLUSMN; 0.10 to 19.70 & PLUSMN; 0.20 & mu;M (for & alpha;-amylase) respectively as compared to standard acarbose with IC50 values of 11.50 & PLUSMN; 0.30 & mu;M (& alpha;-glucosidase) and 12.20 & PLUSMN; 0.30 & mu;M (for & alpha;-amylase).The synthesized analogs also showed significant DPPH and ABTS radical scavenging activities with IC50 values in the range of 1.05 & PLUSMN; 0.05 to 4.56 & PLUSMN; 3.12 & mu;M (for DDPH) and 1.15 & PLUSMN; 0.05 to 4.89 & PLUSMN; 2.89 & mu;M (for ABTS) respectively, incomparison to standard ascorbic acid with IC50 = 1.83 & PLUSMN; 1.32 & mu;M (for DDPH) and 1.84 & PLUSMN; 1.16 & mu;M (for ABTS) respectively. After crucial analysis of varying substitution effects on inhibitory (& alpha;-glucosidase && alpha;-amylase) and radical scavenging (DPPH & ABTS) potentials respectively, the structure-activity relationship (SAR) was established. Through the in silico molecular docking analysis, the ability of the synthesized analogs to inhibit & alpha;-glucosidase and & alpha; -amylase was also examined.There was a good correlation between in vitro and in silico studies for synthesized analogs 5i and 5d Further studies are required to determine whether these potent analogs could be a potential treatment for diabetes disease.