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

Abstract

Inhibition of α-glucosidase and <i>α</i>-amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-<i>b</i>] quinoxalines-carrying thiazole hybrids <b>1-17</b> were created and described using NMR. All analogues were tested for hypoglycaemic effect against STZ-induced diabetes in mice. Compounds <b>4</b>, <b>6</b>, <b>8</b>, and <b>16</b> 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 <i>α</i>-glucosidase and <i>α</i>-amylase enzymes <i>in vitro</i>. The four hybrids <b>4</b>, <b>6</b>, <b>8</b>, and <b>16</b> represented moderate to potent activity with IC₅₀ values 0.982 ± 0.04, to 10.19 ± 0.21 for <i>α</i>-glucosidase inhibition and 17.58 ± 0.74 to 121.6 ± 5.14 μM for <i>α</i>-amylase inhibition when compared to the standard medication acarbose with IC₅₀=0.316 ± 0.02 μM for <i>α</i>-glucosidase inhibition and 31.56 ± 1.33 μM for <i>α</i>-amylase inhibition. Docking studies as well as <i>in silico</i> ADMT were done.