Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.,Journal of Natural Products

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Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.
Journal of Natural Products ( IF 3.3 ) Pub Date : 2021-02-05 , DOI: 10.1021/acs.jnatprod.0c01344
Ying Gao ₁ , Fang-Fang Duan ₁ , Lin Liu ₁ , Xiao-Gang Peng ₁ , Xiang-Gao Meng ₂ , Han-Li Ruan ₁

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Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1–3) and nine 14-membered (4–12), together with seven known analogues (13–19), were obtained from the solid rice-based culture of Podospora sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher’s method, Mo₂(OAc)₄-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12–19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC₅₀ values ranging from 6.0 to 25.1 μM and lipopolysaccharide-induced B cell proliferation with IC₅₀ values ranging from 6.2 to 29.1 μM. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.

中文翻译：

来自波多孢菌属的具有免疫抑制活性的次霉素型间苯二酚酸内酯。

从固体稻米培养物中获得了 12 种新的次霉素型间苯二酚内酯，其中三种 10 元 ( 1 – 3 ) 和 9 种 14 元 ( 4 – 12 )，以及七种已知类似物 ( 13 – 19 )波多孢菌属G214。利用光谱分析阐明了它们的结构，并通过改进的Mosher方法、Mo ₂ (OAc) ₄诱导电子圆二色性实验和单晶X射线衍射确定了它们的绝对构型。化合物1 、 5 、 10和12 – 19对刀豆球蛋白 A 诱导的 T 细胞增殖具有有效的免疫抑制活性，IC ₅₀值范围为 6.0 至 25.1 μM，对脂多糖诱导的 B 细胞增殖具有有效的免疫抑制活性，IC ₅₀值范围为 6.2 至 29.1 μM 。进一步的研究表明， 1通过 JNK 介导的线粒体途径诱导活化 T 细胞凋亡。

更新日期：2021-02-26

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