Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting α-amylase, and α-glucosidase: synthesis, molecular docking, and ADMET studies

Inhibition of alpha-glucosidase and alpha-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-b] quinoxalines-carrying thiazole hybrids 1-17 were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds 4, 6, 8, and 16 were the most potent among the synthesised analogues. These hybrids were examined for their effects on plasma insulin, urea, creatinine, GSH, MDA, ALT, AST, and total cholesterol. Moreover, these compounds were tested against alpha-glucosidase and alpha-amylase enzymes in vitro. The four hybrids 4, 6, 8, and 16 represented moderate to potent activity with IC50 values 0.982 +/- 0.04, to 10.19 +/- 0.21 for alpha-glucosidase inhibition and 17.58 +/- 0.74 to 121.6 +/- 5.14 mu M for alpha-amylase inhibition when compared to the standard medication acarbose with IC50=0.316 +/- 0.02 mu M for alpha-glucosidase inhibition and 31.56 +/- 1.33 mu M for alpha-amylase inhibition. Docking studies as well as in silico ADMT were done.