LAUSR

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.