Scalarane sesterterpenes from a marine sponge of the genus Spongia and their FXR antagonistic activity

J Nat Prod. 2007 Nov;70(11):1691-5. doi: 10.1021/np070024k. Epub 2007 Nov 8.

Abstract

Three new scalarane-based sesterterpenes, 1- 3, were isolated from a marine sponge of the genus Spongia, and their chemical structures were elucidated by analysis of HRMS and 2-D NMR spectra. The isolated compounds 1 and 3 showed inhibition against the farnesoid X-activated receptor (FXR) with IC50 values of 2.4 and 24 microM, respectively. In particular, compound 3 directly inhibited the interaction between FXR and a coactivator peptide (SRC-1) as determined by surface plasmon resonance (SPR) spectroscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / antagonists & inhibitors*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Porifera / chemistry*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Sesterterpenes* / chemistry
  • Sesterterpenes* / isolation & purification
  • Sesterterpenes* / pharmacology
  • Transcription Factors / antagonists & inhibitors*

Substances

  • DNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Sesterterpenes
  • Transcription Factors
  • farnesoid X-activated receptor