Cytotoxic trichothecene-type sesquiterpenes from the sponge-derived fungus Stachybotrys chartarum with tyrosine kinase inhibition

Abstract

Bioassay-guided fractionation of the sponge (Niphates recondite)-associated fungus Stachybotrys chartarum revealed that the EtOAc fraction shows inhibitory effects against tumor cell lines. Chromatographic separation of the active fraction resulted in the isolation of 15 trichothecene-based sesquiterpenes, including four new compounds, namely chartarenes A–D (1–4). The structures of the new compounds were determined on the basis of extensive spectroscopic analysis and chemical conversion. Compounds 1–15 exerted potent or selective inhibition against a panel of tumor cell lines including HCT-116, HepG2, BGC-823, NCI-H1650, and A2780, with IC₅₀ values ranging from 10⁻² to 10 μM. In addition, these compounds showed potent inhibition against tumor-related kinases FGFR3, IGF1R, PDGFRb, and TRKB.