title: Isolation, structure and HIV-1 integrase inhibitory activity of exophillic acid, a novel fungal metabolite from Exophiala pisciphila.
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.
authors.affiliation: Natural Products Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Anne W
authors.initials: AW
authors.lastname: Dombrowski
authors.forename: Jon D
authors.initials: JD
authors.lastname: Polishook
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felock
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D001565:Benzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005093:Exophiala / Q000378:metabolism*; D005285:Fermentation; D005697:Galactosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001565:Benzoates; D005697:Galactosides; D019428:HIV Integrase Inhibitors; C484148:exophillic acid