Suppression of RANKL-Induced Osteoclastogenesis by the Metabolites from the Marine Fungus Aspergillus flocculosus Isolated from a Sponge Stylissa sp

Mar Drugs. 2018 Jan 5;16(1):14. doi: 10.3390/md16010014.

Abstract

A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 1-5 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 1-5 had no anti-proliferative effect on human cancer cell lines up to 30 μg/mL. Among these compounds, aspertetranone D (2) and wasabidienone E (4) exhibited weak osteoclast differentiation inhibitory activity at 10 μg/mL. However, mactanamide (5) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity.

Keywords: Aspergillus flocculosus; TRAP assay; mactanamide; marine fungus; osteoclastogenesis.

MeSH terms

  • Animals
  • Aspergillus / isolation & purification
  • Aspergillus / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Porifera / microbiology*
  • RANK Ligand / metabolism
  • Secondary Metabolism
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology
  • Vietnam

Substances

  • RANK Ligand
  • Sesquiterpenes