Conglobatins B-E: cytotoxic analogues of the C2-symmetric macrodiolide conglobatin

J Antibiot (Tokyo). 2020 Nov;73(11):756-765. doi: 10.1038/s41429-020-0332-3. Epub 2020 Jun 17.

Abstract

Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces, distinct from reported conglobatin producer, Streptomyces conglobatus ATCC 31005. Conglobatins B-E diverge from conglobatin through differing patterns of methylation on the macrodiolide skeleton. The altered methyl positions suggest a deviation from the published biosynthetic pathway, which proposed three successive methylmalonyl-CoA extender unit additions to the conglobatin monomer. Conglobatins B1, C1 and C2 exhibited more potent cytotoxic activity selectively against the NS-1 myeloma cell line (IC50 0.084, 1.05 and 0.45 µg ml-1, respectively) compared with conglobatin (IC50 1.39 µg ml-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor / drug effects
  • Cytotoxins / chemistry
  • Cytotoxins / isolation & purification*
  • Cytotoxins / pharmacology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oxazoles / chemistry
  • Oxazoles / isolation & purification*
  • Streptomyces / chemistry

Substances

  • Cytotoxins
  • Oxazoles
  • conglobatin