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

Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (1-3) and nine 14-membered (4-12), together with seven known analogues (13-19), 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, Mo-2 (OAc)(4)-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds 1, 5, 10, and 12-19 exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC50 values ranging from 6.0 to 25.1 mu M and lipopolysaccharide-induced B cell proliferation with IC50 values ranging from 6.2 to 29.1 mu M. Further studies revealed that 1 induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.

Automated summary

Twelve new hypothemycin-type resorcylic acid lactones were isolated from Podospora sp. G214. Compounds 1 exhibited potent immunosuppressive activities by inducing apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.