Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts

Bioorg Med Chem Lett. 2017 Nov 15;27(22):4975-4978. doi: 10.1016/j.bmcl.2017.10.017. Epub 2017 Oct 9.

Abstract

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (-)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (-)-6-epi-notoamide T was the most potent inhibitor with an IC50 value of 1.7μM.

Keywords: Aspergillus; Enantiomer; Fungus; Notoamide; Osteoclastogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Fungi / drug effects
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / pharmacology
  • Inhibitory Concentration 50
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • RANK Ligand / metabolism*
  • RAW 264.7 Cells
  • Stereoisomerism

Substances

  • Indole Alkaloids
  • RANK Ligand
  • notoamide B
  • notoamide T