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

J Nat Prod. 2015 Oct 23;78(10):2461-70. doi: 10.1021/acs.jnatprod.5b00578. Epub 2015 Sep 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Down-Regulation
  • Emericella / chemistry*
  • Fungi
  • Hep G2 Cells
  • Humans
  • Marine Biology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Oxepins
  • Polyketides / chemistry
  • Polyketides / isolation & purification*
  • Porifera / microbiology*
  • Terpenes
  • X-Ray Diffraction
  • Xanthones / chemistry
  • Xanthones / isolation & purification*

Substances

  • 19-O-methyl-22-methoxypre-shamixanthone
  • Oxepins
  • Polyketides
  • Terpenes
  • Xanthones
  • varioxepine A