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

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.