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Varioxiranols A–G and 19-O-Methyl-22-methoxypre-shamixanthone, PKS and Hybrid PKS-Derived Metabolites from a Sponge-Associated Emericella variecolor Fungus

Wu, Qi, Wu, Chongming, Long, Hailin, Chen, Ran, Liu, Dong, Proksch, Peter, Guo, Peng, Lin, Wenhan
Journal of natural products 2015 v.78 no.10 pp. 2461-2470
Emericella, X-ray diffraction, benzyl alcohol, cholesterol, cytotoxicity, fungi, gene expression regulation, genes, human cell lines, metabolites, polyketides, quantitative polymerase chain reaction, spectral analysis, transcription factors, triacylglycerols, xanthone
Chemical examination of a sponge (Cinachyrella sp.)-associated Emericella variecolor fungus resulted in the isolation of seven new polyketide derivatives, namely, varioxiranols A–G (1–7), and a new hybrid PKS-isoprenoid metabolite, 19-O-methyl-22-methoxypre-shamixanthone (8), together with nine known analogues. Their structures were elucidated on the basis of extensive spectroscopic analyses, including ECD effects, Mosher’s method, X-ray diffraction, and chemical conversion for the determination of absolute configurations. Varioxiranols F and G were found for the first time to link a xanthone moiety with a benzyl alcohol via an ether bond, while the dioxolanone group of 5 is unusual in nature. A cell-based lipid-lowering assay revealed that pre-shamixanthone (12) exerted significant inhibition against lipid accumulation in HepG2 cells without cytotoxic effects, accompanying the potent reduction of total cholesterol and triglycerides. Real-time quantitative PCR indicated that pre-shamixanthone (12) mediated the reduction of lipid accumulation related to the down-regulation of the expression of the key lipogenic transcriptional factor SREBP-1c and its downstream genes encoding FAS and ACC.