Isolation of Coralmycins A and B, Potent Anti-Gram Negative Compounds from the Myxobacteria Corallococcus coralloides M23

J Nat Prod. 2016 Sep 23;79(9):2223-8. doi: 10.1021/acs.jnatprod.6b00294. Epub 2016 Sep 6.

Abstract

Two new potent anti-Gram negative compounds, coralmycins A (1) and B (2), were isolated from cultures of the myxobacteria Corallococcus coralloides M23, together with another derivative (3) that was identified as the very recently reported cystobactamid 919-2. Their structures including the relative stereochemistry were elucidated by interpretation of spectroscopic, optical rotation, and CD data. The relative stereochemistry of 3 was revised to "S*R*" by NMR analysis. The antibacterial activity of 1 was most potent against Gram-negative pathogens, including Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumanii, and Klebsiella pneumoniae, with MICs of 0.1-4 μg/mL; these MICs were 4-10 and 40-100 times stronger than the antibacterial activities of 3 and 2, respectively. Thus, these data indicated that the β-methoxyasparagine unit and the hydroxy group of the benzoic acid unit were critical for antibacterial activity.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / pharmacology*
  • Asparagine / analogs & derivatives
  • Asparagine / chemistry
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / chemistry
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification*
  • Depsipeptides / pharmacology
  • Escherichia coli / drug effects
  • Hep G2 Cells
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Myxococcales / chemistry*
  • Nitro Compounds / chemistry
  • Nuclear Magnetic Resonance, Biomolecular
  • Pseudomonas aeruginosa / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Depsipeptides
  • Nitro Compounds
  • coralmycin A
  • coralmycin B
  • cystobactamid 919-2
  • Aspartic Acid
  • Asparagine