Sàng lọc in silico các flavonoid có khả năng ức chế enzym α-amylase và α-glucosidase hướng điều trị đái tháo đường type 2

Alkaloid, glycoside, polysaccharide, phenolic acid…and especially flavonoids (e.g. morin, luteolin, baicalein, rutin, myricetin…) were known as inhibitors of α-glucosidase and/or α-amylase. In this study, 1041 flavonoids were screened based on molecular docking using Autodock Vina for their α-glucosidase and/or α-amylase enzymes inhibitory effects to support in vitro test as well as to guide the synthesis of potential flavonoid. Results showed that in silico screening selected 11 potential inhibitors belonging to flavonones, flavones, and chalcones groups in terms of binding affinities or docking scores of -10,9 kcal.mol-1 to -8,0 kcal.mol-1 for α-amylase) and of -8,9 kcal.mol-1 to -8,0 kcal.mol-1 for α-glucosidase). Moreover, their structure-binding interactions relationships of flavonoids and both enzymes were investigated. It could be inferred that hydroxyl and prenyl groups played important roles in forming the interactions with key residues of the two enzymes. Hydroxyl group in rings A and B bonded with key residues Asp197, Glu233 of α-amylase and Asp542, Asp203, Arg526 of α-glucosidase through hydrogen bonds. In addition to, prenyl group at the -6 site of ring A and 5’ site of ring B created many hydrophobic interactions with important residues such as His201, Trp59 (α-amylase) and His600, Phe575, Tyr299, Trp441(α-glucosidase).
Keywords: α-amylase, α-glucosidase, type 2 diabetes, molecular docking, in silico screening.