np0c01344_si_010.cif (599.44 kB)

Hypothemycin-Type Resorcylic Acid Lactones with Immunosuppressive Activities from a Podospora sp.

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posted on 05.02.2021, 19:38 by Ying Gao, Fang-Fang Duan, Lin Liu, Xiao-Gang Peng, Xiang-Gao Meng, Han-Li Ruan
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.