Synthesis, in vitro evaluation and molecular docking studies of novel amide linked triazolyl glycoconjugates as new inhibitors of α-glucosidase

Abstract 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 (IC 50  = 156.06 μM), 4f (IC 50  = 147.94 μM), 4k (IC 50  = 127.71 μM) and 4l (IC 50  = 121.33 μM) were identified as the most potent inhibitors for α-glucosidase as compared to acarbose (IC 50  = 130.98 μM) 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 −8.5 kcal/mol respectively, compared to that of acarbose (−8.9 kcal/mol). The results suggest that the N -substituted amide linked triazole glycoconjugates can reasonably mimic the substrates for the yeast α-glucosidase.