The Halicylindramides, Farnesoid X Receptor Antagonizing Depsipeptides from a Petrosia sp. Marine Sponge Collected in Korea

J Nat Prod. 2016 Mar 25;79(3):499-506. doi: 10.1021/acs.jnatprod.5b00871. Epub 2016 Jan 28.

Abstract

Three new structurally related depsipeptides, halicylindramides F-H (1-3), and two known halicylindramides were isolated from a Petrosia sp. marine sponge collected off the shore of Youngdeok-Gun, East Sea, Republic of Korea. Their planar structures were elucidated by extensive spectroscopic data analyses including 1D and 2D NMR data as well as MS data. The absolute configurations of halicylindramides F-H (1-3) were determined by Marfey's method in combination with Edman degradation. The absolute configurations at C-4 of the dioxyindolyl alanine (Dioia) residues of halicylindramides G (2) and H (3) were determined as 4S and 4R, respectively, based on ECD spectroscopy. The C-2 configurations of Dioia in 2 and 3 were speculated to both be 2R based on the shared biogenesis of the halicylindramides. Halicylindramides F (1), A (4), and C (5) showed human farnesoid X receptor (hFXR) antagonistic activities, but did not bind directly to hFXR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depsipeptides* / chemistry
  • Depsipeptides* / isolation & purification
  • Depsipeptides* / pharmacology
  • Humans
  • Marine Biology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Petrosia / chemistry*
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Republic of Korea

Substances

  • Depsipeptides
  • Receptors, Cytoplasmic and Nuclear
  • halicylindramide A
  • halicylindramide G
  • halicylindramide H
  • farnesoid X-activated receptor