Curtachalasins, immunosuppressive agents from the endophytic fungus Xylaria cf. curta

Abstract

Eleven new cytochalasins, curtachalasins F–P (1–11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F–P, A–C, and E (1–15), compounds 1, 3–6, 8–13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC₅₀ value of 2.42 μM) and compound 10 has selective inhibition on T-cell proliferation (IC₅₀ value of 12.15 μM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.