Gao Ying, Duan Fangfang, Chang Jinling, Meng Xianggao, Ruan Hanli
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Wuhan 430030, People's Republic of China.
College of Chemistry, Central China Normal University, Wuhan 430079, People's Republic of China.
Bioorg Chem. 2022 Jan;118:105482. doi: 10.1016/j.bioorg.2021.105482. Epub 2021 Nov 11.
Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo(OAc)- and Rh(OCOCF)-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC values of 14.5-21.9 μM, and B cell proliferation with IC values of 22.3-36.5 μM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.
从地榆根中内生真菌Podospora sp. G214中鉴定出12种未描述的腐霉素型间苯二酚酸内酯（Podomycins A-L，1-12）。通过光谱数据、X射线晶体学、改良的莫舍尔方法以及钼（乙酸根）和铑（三氟乙酸根）诱导的电子圆二色性（ICD）实验确定了它们的结构。Podomycins A-C（1-3）代表了第一类具有13元大环内酯环的天然间苯二酚酸内酯，而4-12是重排的甲氧基羰基取代的间苯二酚酸内酯。在生物学上，化合物2、6、8、10和12对T细胞增殖显示出免疫抑制活性，IC值为14.5-21.9 μM，对B细胞增殖的IC值分别为22.3-36.5 μM。进一步的作用机制研究表明，腐霉素F（6）通过MAPKs/AKT途径明显诱导活化T细胞凋亡。
