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Cytotoxic trichothecene-type sesquiterpenes from the sponge-derived fungus Stachybotrys chartarum with tyrosine kinase inhibition†
Yong Li,Dong Liu,Zhongbin Cheng,Peter Proksch,Wenhan Lin
RSC Advances Pub Date : 01/23/2017 00:00:00 , DOI:10.1039/C6RA26956G
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.

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