Acroeremophilanes A–I, eremophilane-type sesquiterpenoids from the Sinomenium acutum-derived symbiotic fungus Acrocalymma cycadis

This study separated nine previously undescribed highly oxygenated eremophilane sesquiterpenoids, designated as acroeremophilanes A–I (1–9), as well as three identified analogs (10–12), in the symbiotic fungus Acrocalymma cycadis derived from Sinomenium acutum. Structural elucidation of the metabolites was achieved using 1D and 2D NMR; HR-ESI-TOF-MS; single-crystal X-ray diffraction; and ECD spectra calculations. Notably, acroeremophilane A (1) was identified as an unusual chlorinated nor-eremophilane sesquiterpenoid incorporating an α,β-unsaturated ketone unit with an enol fragment. Acroeremophilanes F–H (6–8) were characterized as rare glycosylated eremophilane sesquiterpenoids derived from the symbiotic fungus. The in vitro cytotoxicities showed that C-1 substituted chlorinated eremophilane sesquiterpenoids displayed obvious cytotoxicity, in which acroeremophilane C (3) exhibited potent cytotoxicity to HeLa and A549 cells, and IC₅₀ values were 2.89 and 4.55 μM, separately. The results of the apoptosis assays indicated that compound 3 primarily induces apoptotic cell death.