title: Varioxiranols A-G and 19-O-Methyl-22-methoxypre-shamixanthone, PKS and Hybrid PKS-Derived Metabolites from a Sponge-Associated Emericella variecolor Fungus.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing 100193, People's Republic of China.
authors.forename: Chongming
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Long
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing 100193, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine University , 40225 Duesseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing 100193, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University , Beijing 100191, People's Republic of China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
mesh_terms: D000818:Animals; D015536:Down-Regulation; D032842:Emericella / Q000737:chemistry*; D005658:Fungi; D056945:Hep G2 Cells; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010082:Oxepins; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification*; D011161:Porifera / Q000382:microbiology*; D013729:Terpenes; D014961:X-Ray Diffraction; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: C000604839:19-O-methyl-22-methoxypre-shamixanthone; D010082:Oxepins; D061065:Polyketides; D013729:Terpenes; D044004:Xanthones; C000599274:varioxepine A