Isolation, structure and HIV-1 integrase inhibitory activity of exophillic acid, a novel fungal metabolite from Exophiala pisciphila

J Antibiot (Tokyo). 2003 Dec;56(12):1018-23. doi: 10.7164/antibiotics.56.1018.

Abstract

HIV-1 integrase is one of the three enzymes that are critical for replication and spread of HIV and its inhibition is one of the most promising new drug targets for anti-retroviral therapy with potential advantage over existing therapies. This paper describes the isolation and structure elucidation of exophillic acid, a novel dimeric 2,4-dihydroxy alkyl benzoic acid, derived from Exophiala pisciphila, a fungus isolated from a soil sample collected in Georgia, USA. Exophillic acid (1) and aquastatin A (2), a related compound, inhibited the strand transfer reaction of HIV-1 integrase with IC50 values of 68 and 50 microM, respectively.

MeSH terms

  • Benzoates / chemistry
  • Benzoates / isolation & purification
  • Benzoates / pharmacology*
  • Chromatography, High Pressure Liquid
  • Exophiala / metabolism*
  • Fermentation
  • Galactosides / chemistry
  • Galactosides / isolation & purification
  • Galactosides / pharmacology*
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / isolation & purification
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / enzymology*
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Benzoates
  • Galactosides
  • HIV Integrase Inhibitors
  • exophillic acid