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

• Published in: Journal of antibiotics Vol. 56; no. 12; p. 1018
• Main Authors: Ondeyka, John G, Zink, Deborah L, Dombrowski, Anne W, Polishook, Jon D, Felock, Peter J, Hazuda, Daria J, Singh, Sheo B
• Format: Journal Article
• Language: English
• Published: Japan 01-12-2003
• Subjects: 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
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.56.1018

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.