Pyrronazols, metabolites from the myxobacteria Nannocystis pusilla and N. exedens, are unusual chlorinated pyrone-oxazole-pyrroles

J Nat Prod. 2014 Feb 28;77(2):320-6. doi: 10.1021/np400877r. Epub 2014 Jan 24.

Abstract

The chlorinated pyrrole-oxazole-pyrones pyrronazol A (1), pyrronazol A2 (2), and pyrronazol B (3) were isolated from Nannocystis pusilla strain Ari7, and two chlorinated pyrrole-oxazole isomers, pyrronazols C1 (4) and C2 (5), were isolated from N. pusilla strain Na a174. HRESIMS, NMR, and X-ray crystallographic analysis was used in the structure elucidation including the absolute configuration of pyrronazol A (1). In addition to pyrronazols, 1,6-phenazine-diol (6) and its glycosyl derivative, 1-hydroxyphenazin-6-yl-α-d-arabinofuranoside (7), were isolated and identified from the culture broth of N. pusilla strain Ari7. When tested for biological activity against bacteria, fungi, and yeasts, 1 showed weak antifungal activity against Mucor hiemalis (MIC 33.3 μg/mL) but no antibacterial activity, while 6 showed weak antibacterial and antifungal activity (MIC 33.3 μg/mL) against some of the strains tested. In cell culture experiments 1 showed no significant cytotoxicity, while 6 was active against several cell lines, especially the human ovarian carcinoma cells SK-OV-3 (LD50 2.59 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Structure
  • Mucor / drug effects
  • Myxococcales / chemistry*
  • Oxazoles / chemistry
  • Oxazoles / isolation & purification*
  • Oxazoles / pharmacology
  • Pyrones / chemistry
  • Pyrones / isolation & purification*
  • Pyrones / pharmacology
  • Pyrroles / chemistry
  • Pyrroles / isolation & purification*
  • Pyrroles / pharmacology

Substances

  • Antifungal Agents
  • Oxazoles
  • Pyrones
  • Pyrroles