Novel Bioactive Paulomycin Derivatives Produced by Streptomyces albus J1074

Molecules. 2017 Oct 18;22(10):1758. doi: 10.3390/molecules22101758.

Abstract

Four novel paulomycin derivatives have been isolated from S. albus J1074 grown in MFE culture medium. These compounds are structural analogs of antibiotics 273a and 273a containing a thiazole moiety, probably originated through an intramolecular Michael addition. The novel, thiazole, moiety-containing paulomycins show a lower antibiotic activity than paulomycins A and B against Gram-positive bacteria. However, two of them show an improved activity against Gram-negative bacteria. In addition, the four novel compounds are more stable in culture than paulomycins A and B. Thus, the presence of an N-acetyl-l-cysteine moiety linked to the carbon atom of the paulic acid isothiocyanate moiety, via a thioester bond, and the subsequent intramolecular cyclization of the paulic acid to generate a thiazole heterocycle confer to paulomycins a higher structural stability that otherwise will conduce to paulomycin degradation and into inactive paulomenols.

Keywords: antibiotic 273a2; paulic acid; paulomenol; structural analogue; thiazole moiety.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / isolation & purification*
  • Anti-Bacterial Agents / therapeutic use
  • Cyclohexenes / chemistry
  • Cyclohexenes / pharmacology
  • Disaccharides / chemistry
  • Disaccharides / pharmacology
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / pathogenicity
  • Humans
  • Streptomyces / chemistry*
  • Thiazoles / chemistry*
  • Thiazoles / isolation & purification
  • Thiazoles / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Cyclohexenes
  • Disaccharides
  • Thiazoles
  • paulomenol B
  • paulomycin A