Indoloditerpenes from a marine-derived fungal strain of Dichotomomyces cejpii with antagonistic activity at GPR18 and cannabinoid receptors

J Nat Prod. 2014 Mar 28;77(3):673-7. doi: 10.1021/np400850g. Epub 2014 Jan 28.

Abstract

A marine-derived strain of Dichotomomyces cejpii produces the new compounds emindole SB beta-mannoside (1) and 27-O-methylasporyzin C (2), as well as the known indoloditerpenes JBIR-03 (3) and emindole SB (4). Indole derivative 1 was found to be a CB2 antagonist, while 2 was identified as the first selective GPR18 antagonist with an indole structure. Compound 4 was found to be a nonselective CB1/CB2 antagonist. The new natural indole derivatives may serve as lead structures for the development of GPR18- and CB receptor-blocking drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / drug effects
  • Ascomycota / chemistry*
  • Australia
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Humans
  • Indoles / chemistry
  • Indoles / isolation & purification*
  • Indoles / pharmacology*
  • Mannosides / chemistry
  • Mannosides / isolation & purification*
  • Mannosides / pharmacology*
  • Marine Biology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • beta-Arrestins

Substances

  • 27-O-methylasporyzin C
  • Arrestins
  • Diterpenes
  • GPR18 protein, human
  • Indoles
  • JBIR-03
  • Mannosides
  • Receptor, Cannabinoid, CB2
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • emindole SB beta-mannoside