Novel Anthrone-Furanone Hybrids and Monomers with Antidrug-Resistant Activity from the Biocontrol Fungus Clonostachys rosea.

Fifteen new metabolites were isolated from Clonostachys rosea, a biocontrol fungus derived from Taxus yunnanensis. Among these, clonostachydimers A and B (14-15) are unprecedented anthrone-furanone hybrid dimers with a unique 6/6/6/6/5 pentacyclic framework, presumably biosynthesized via a [4 + 2] cycloaddition reaction. Their structures and absolute configurations were established by spectroscopic analyses, X-ray crystallography, ECD calculations, Snatzke's method, and DP4+ analysis. Bioassays indicated that several metabolites exhibited significant antimicrobial activity against drug-resistant pathogens as well as cytotoxic activity. Compound 3 showed potent cytotoxicity against A549/Taxol cells (IC50 = 0.542 μM), exceeding that of doxorubicin and paclitaxel, while also displaying activity against MRSA and Candida albicans. Molecular docking suggested potential dual targeting of Topoisomerase II and P-glycoprotein, supporting its activity against paclitaxel-resistant cells.