During a search for new α-glucosidase and protein tyrosine phosphatase 1B inhibitors from fungal sources, eight new secondary metabolites, including two anthranilic acid-derived peptides (1 and 2), four glycosylated anthraquinones (3-6), 4-isoprenylravenelin (7), and a dimer of 5,8-dihydroxy-4-methoxy-α-tetralone (8), along with four known compounds (9-12), were isolated from solid rice-based cultures of Malbranchea circinata. The structural elucidation of these metabolites was performed using 1D and 2D NMR techniques and DFT-calculated chemical shifts. Compounds 1-3, 9, and 10 showed inhibitory activity to yeast α-glucosidase (αGHY), with IC50 values ranging from 57.4 to 261.3 μM (IC50 acarbose = 585.8 μM). The effect of 10 (10.0 mg/kg) was corroborated in vivo using a sucrose tolerance test in normoglucemic mice. The most active compounds against PTP-1B were 8-10, with IC50 values from 10.9 to 15.3 μM (IC50 ursolic acid = 27.8 μM). Docking analysis of the active compounds into the crystal structures of αGHY and PTP-1B predicted that all compounds bind to the catalytic domains of the enzymes. Together, these results showed that M. circinata is a potential source of antidiabetic drug leads.

中文翻译：

---

来自 Malbranchea circinata 的 α-葡萄糖苷酶和蛋白质酪氨酸磷酸酶 1B 抑制剂。

在从真菌来源寻找新的 α-葡萄糖苷酶和蛋白酪氨酸磷酸酶 1B 抑制剂的过程中，发现了八种新的次级代谢物，包括两种邻氨基苯甲酸衍生肽（1 和 2）、四种糖基化蒽醌 (3-6)、4-异戊二烯基拉维林 (7) )、5,8-二羟基-4-甲氧基-α-四氢萘酮 (8) 的二聚体以及四种已知化合物 (9-12)，是从 Malbranchea circinata 的基于水稻的固体培养物中分离出来的。这些代谢物的结构解析是使用一维和二维核磁共振技术和 DFT 计算的化学位移进行的。化合物 1-3、9 和 10 对酵母 α-葡萄糖苷酶 (αGHY) 显示出抑制活性，IC50 值范围为 57.4 至 261.3 μM（IC50 阿卡波糖 = 585.8 μM）。10 (10.0 mg/kg) 的作用在血糖正常小鼠中使用蔗糖耐受性试验在体内得到证实。对 PTP-1B 最具活性的化合物为 8-10，IC50 值为 10.9 至 15.3 μM（IC50 熊果酸 = 27.8 μM）。将活性化合物与 αGHY 和 PTP-1B 的晶体结构对接分析预测，所有化合物都与酶的催化结构域结合。总之，这些结果表明 M. circinata 是抗糖尿病药物线索的潜在来源。