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

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 mu M, 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.