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Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.
Journal of Natural Products ( IF 5.1 ) 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
Affiliation  

Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (13) and nine 14-membered (412), together with seven known analogues (1319), 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 1219 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 Podospora sp. 的具有免疫抑制活性的 Hypothemycin 型间苯二酸内酯。

从基于水稻的固体培养物中获得了12 种新的hypothemycin 型间苯二酸内酯,3 种 10 元 ( 13 ) 和 9 种 14 元 ( 412 ),以及 7 种已知类似物 ( 1319 )。足孢菌属 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 射线衍射确定了绝对构型。化合物1510,和12 - 19对刀豆蛋白 A 诱导的 T 细胞增殖表现出有效的免疫抑制活性,IC 50值范围为 6.0 至 25.1 μM,以及脂多糖诱导的 B 细胞增殖,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的 T 细胞凋亡。
更新日期:2021-02-26
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