α-Glucosidase is the key enzyme on carbohydrate metabolism, and its bioactive inhibitors are supposed to be an effective therapeutic for type 2 diabetes mellitus. During our continuing study for discovering α-glucosidase inhibitors, a fungus GDZZ-G2 which is derived from a medicinal plant Callicarpa kwangtungensis Chun, exhibited significant inhibition on α-glucosidase. The strain was identified as Fusarium incarnatum by morphological and molecular methods. Further bioassay-guided fractionation result in six known secondary metabolites (1-6). All the compounds except 4 were isolated from F. incarnatum for the first time. Among them, an anthraquinonoid (S)-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione (compound 1) exhibited strong inhibitory effect against α-glucosidase (IC50 = 77.67 ± 0.67 μΜ), compared with acarbose (IC50 = 711.8 ± 5 μΜ). An enzyme kinetics analysis revealed that compound 1 was an uncompetitive inhibitor. Besides, docking simulations predicted that compound 1 inhibited α-glucosidase substrate complex by binding Gln322, Gly306, Thr307, and Ser329 through hydrogen-bond interactions. Our findings suggested that compound 1 can be considered a lead compound for further modifications and the development of a new effective drug candidate in the treatment of type 2 diabetes mellitus.
Keywords: Fusarium incarnatum; anthraquinonoid; molecular docking; α-glucosidase inhibitors.
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