Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

J Antibiot (Tokyo). 2014 Jan;67(1):121-6. doi: 10.1038/ja.2013.115. Epub 2013 Nov 13.

Abstract

A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1-5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis, Bacillus subtilis, Pseudomonas aeruginosa and Burkholderia cepacia. Compounds 2-5 showed varying degrees of activity against human cells, M. tuberculosis and B. subtilis in the low μM to mid nM range but were inactive against the other strains, while 1 lacking digitoxose was inactive. Very slight structural changes in 2-5 led to varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Bacteria / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • Macrolides / chemistry
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Mollusca / microbiology*
  • Polyketides / chemistry
  • Polyketides / isolation & purification
  • Polyketides / pharmacology*
  • Spectrum Analysis
  • Streptomyces / chemistry*
  • Streptomyces / genetics
  • Streptomyces / isolation & purification
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Macrolides
  • Polyketides

Associated data

  • GENBANK/KF137580