Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
J Nat Prod. 2021 Feb 26;84(2):483-494. doi: 10.1021/acs.jnatprod.0c01344. Epub 2021 Feb 5.
Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (-) and nine 14-membered (-), together with seven known analogues (-), were obtained from the solid rice-based culture of sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo(OAc)-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds , , , and - exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC values ranging from 6.0 to 25.1 μM and lipopolysaccharide-induced B cell proliferation with IC values ranging from 6.2 to 29.1 μM. Further studies revealed that induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.
从 sp. G214 的固态大米培养基中分离得到了 12 种新型的 Hypothemycin 型缩酚酸内酯，其中 3 种为 10 元环（-）和 9 种 14 元环（-），以及 7 种已知类似物（-）。通过光谱分析阐明了它们的结构，并通过改进的 Mosher 法、Mo(OAc)-诱导的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 、 、 、和 - 对刀豆蛋白 A 诱导的 T 细胞增殖具有很强的免疫抑制活性，IC 值范围为 6.0 到 25.1 μM，对脂多糖诱导的 B 细胞增殖具有很强的抑制活性，IC 值范围为 6.2 到 29.1 μM。进一步的研究表明， 通过 JNK 介导的线粒体途径诱导活化 T 细胞凋亡。
