Anti-Cryptococcus Phenalenones and Cyclic Tetrapeptides from Auxarthron pseudauxarthron

J Nat Prod. 2017 Jul 28;80(7):2101-2109. doi: 10.1021/acs.jnatprod.7b00341. Epub 2017 Jun 28.

Abstract

Auxarthrones A-E (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides A (7) and B (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus Auxarthron pseudauxarthron. Auxarthrones C (3) and E (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. Formation of 1-5 was found to be dependent on the solvent used for culture extraction. The structures of these new compounds were elucidated primarily by analysis of NMR and MS data. Auxarthrone A (1) was obtained as a mixture of chromatographically inseparable racemic diastereomers (1a and 1b) that cocrystallized, enabling confirmation of their structures by X-ray crystallography. The absolute configurations of 7 and 8 were assigned by analysis of their acid hydrolysates using Marfey's method. Compound 1 displayed moderate antifungal activity against Cryptococcus neoformans and Candida albicans, but did not affect human cancer cell lines.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology*
  • Ascomycota / chemistry*
  • Breast Neoplasms / drug therapy
  • Candida albicans / drug effects
  • Cryptococcus neoformans / drug effects*
  • Crystallography, X-Ray
  • Female
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology*
  • Phenalenes / chemistry
  • Phenalenes / isolation & purification*
  • Phenalenes / pharmacology*

Substances

  • Antifungal Agents
  • Peptides, Cyclic
  • Phenalenes
  • phenalen-1-one