Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces the production of anti-inflammatory cyclodepsipeptides from Beauveria felina

J Nat Prod. 2013 Jul 26;76(7):1260-6. doi: 10.1021/np400143j. Epub 2013 Jul 3.

Abstract

The addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid to a culture of the filamentous fungus Beauveria felina significantly changed its secondary metabolite profile and led to the isolation of eight compounds, including three new cyclodepsipeptides, desmethylisaridin E (1), desmethylisaridin C2 (2), and isaridin F (3), along with five known cyclodepsipeptide compounds. Isaridin F (3) possesses a cyclodepsipeptide ring with N-methylbutyric acid, which is rare in natural peptides. Absolute configurations of the new cyclodepsipeptides were achieved by Marfey's method. The anti-inflammatory activity of the isolated compounds was investigated through evaluating their effect on superoxide anion production and elastase release by FMLP-induced human neutrophils. Among the tested compounds, desmethylisaridin E (1) inhibited superoxide anion production and desmethylisaridin C2 (2) inhibited elastase release, with IC50 values of 10.00 ± 0.80 and 10.01 ± 0.46 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Beauveria / chemistry*
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification*
  • Depsipeptides / pharmacology*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neutrophils / drug effects
  • Nuclear Magnetic Resonance, Biomolecular
  • Superoxides / metabolism
  • Vorinostat

Substances

  • Anti-Inflammatory Agents
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • desmethylisaridin C2
  • desmethylisaridin E
  • isaridin F
  • Superoxides
  • Vorinostat