Synthesis and studies of thiazolidinedione-isatin hybrids as α-glucosidase inhibitors for management of diabetes

Aim: Keeping in view the side effects associated with clinically used alpha-glucosidase inhibitors, novel thiazolidinedione-isatin hybrids were synthesized and evaluated by in vitro, in vivo and in silico procedures. Materials & methods: Biological evaluation, cytotoxicity assessment, molecular docking, binding free energy calculations and molecular dynamics studies were performed for hybrids. Results: The most potent inhibitor A-10 (IC50 = 24.73 +/- 0.93 mu M) was competitive in manner and observed as non-cytotoxic. A-10 possessed higher efficacy than the standard drug (acarbose) during in vivo biological testing. Conclusion: The enzyme inhibitory potential and safety profile of synthetic molecules was recognized after in vitro, in vivo, in silico and cytotoxicity studies. Further structural optimization of A-10 can offer potential hit molecules suitable for future investigations.

Automated summary

Novel thiazolidinedione-isatin hybrids were synthesized and evaluated for their α-glucosidase inhibitory potential, with A-10 showing competitive inhibition and higher efficacy than acarbose. Further structural optimization of A-10 may lead to potential hit molecules for future investigations, as demonstrated in in vitro, in vivo, in silico, and cytotoxicity studies.