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.

中文翻译：

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Fusarium incarnatum GDZZ-G2产生的蒽醌类化合物的α-葡萄糖苷酶抑制作用

α-葡萄糖苷酶是碳水化合物代谢的关键酶，其生物活性抑制剂被认为是治疗 2 型糖尿病的有效药物。在我们继续研究发现 α-葡萄糖苷酶抑制剂的过程中，一种源自药用植物Callicarpa kwangtungensis Chun 的真菌 GDZZ-G2 对 α-葡萄糖苷酶具有显着的抑制作用。通过形态学和分子学方法鉴定该菌株为Fusarium incarnatum 。进一步的生物测定指导分馏产生六种已知的次级代谢物( 1-6 )。除4之外的所有化合物均从F中分离出来。第一次化身。其中，蒽醌类（ 与阿卡波糖相比，S )-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione（化合物1）对 α-葡糖苷酶具有很强的抑制作用（IC ₅₀ = 77.67 ± 0.67 μM） (IC ₅₀  = 711.8 ± 5 μM)。酶动力学分析表明化合物1是一种非竞争性抑制剂。此外，对接模拟预测化合物1通过氢键相互作用结合 Gln322、Gly306、Thr307 和 Ser329 来抑制 α-葡萄糖苷酶底物复合物。我们的研究结果表明，化合物1可被视为一种先导化合物，可用于进一步修饰和开发治疗 2 型糖尿病的新有效候选药物。