Resorcylic acid lactones from a Podospora sp. that induce apoptosis in activated T cells through MAPKs/AKT pathway

作者：Gao, Ying; Duan, Fangfang; Chang, Jinling; Meng, Xianggao; Ruan, Hanli^*

来源：Bioorganic Chemistry, 2022, 118: 105482.

DOI：10.1016/j.bioorg.2021.105482

• Resorcylic acid lactones
• Podospora sp.
• Immunosuppressive activity
• MAPKs/AKT pathway

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-2(OAc)(4)- and Rh-2(OCOCF3)(4)-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macmlactone 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 IC50 values of 14.5-21.9 mu M, and B cell proliferation with IC50 values of 22.3-36.5 mu M, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.

• 单位
  华中科技大学