A series of N-substituted amide linked triazolyl β-d-glucopyranoside derivatives (4a-l) were synthesized and their in vitro inhibitory activity against yeast α-glucosidase enzyme [EC.3.2.1.20] was assessed. Compounds 4e (IC50=156.06μM), 4f (IC50=147.94μM), 4k (IC50=127.71μM) and 4l (IC50=121.33μM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC50=130.98μM) under the same in vitro experimental conditions. Kinetic study showed that both 4e and 4f inhibit the enzyme in a competitive manner with p-nitrophenyl α-d-glucopyranoside as substrate. Molecular docking studies of 4e, 4f, 4k and 4l were also carried out using homology model of α-glucosidase to find out the binding modes responsible for the inhibitory activity. This study revealed that the binding affinity of compounds 4e, 4f, 4k and 4l for α-glucosidase were -8.2, -8.6, -8.3 and -8.5kcal/mol respectively, compared to that of acarbose (-8.9kcal/mol). The results suggest that the N-substituted amide linked triazole glycoconjugates can reasonably mimic the substrates for the yeast α-glucosidase.
Keywords: Amide linked glucopyranoside; Diabetes; Docking studies; Glycoconjugate; Triazole; α-Glucosidase.
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