Cinnabaramides A-G: analogues of lactacystin and salinosporamide from a terrestrial streptomycete

J Nat Prod. 2007 Feb;70(2):246-52. doi: 10.1021/np060162u. Epub 2007 Jan 24.

Abstract

The cinnabaramides A-G (1-7) were isolated from a terrestrial strain of Streptomyces as potent and selective inhibitors of the human 20S proteasome. Their chemical and biological properties resemble those of salinosporamide A, a recently identified lead compound from an obligate marine actinomycete, which is currently under development as an anticancer agent. Cinnabaramides F and G (6, 7) combine essential structural features of salinosporamide A and lactacystin and show about equal potency in vitro, with IC50 values in the 1 nM range. The properties and phylogenetic position of the producer organism, the production and isolation of compounds 1-7, their structure elucidation by MS and NMR, and their biological activities are reported. Additionally, an X-ray crystal structure was obtained from cinnabaramide A (1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / blood
  • Acetylcysteine / chemistry
  • Acetylcysteine / isolation & purification
  • Acetylcysteine / pharmacology
  • Crystallography, X-Ray
  • Humans
  • Lactones* / blood
  • Lactones* / isolation & purification
  • Lactones* / pharmacology
  • Molecular Conformation
  • Molecular Structure
  • Proteasome Inhibitors*
  • Pyrroles* / blood
  • Pyrroles* / isolation & purification
  • Pyrroles* / pharmacology
  • Streptomyces / chemistry*

Substances

  • Lactones
  • Proteasome Inhibitors
  • Pyrroles
  • lactacystin
  • marizomib
  • Acetylcysteine