Isolation, structure and HIV-1 integrase inhibitory activity of exophillic acid, a novel fungal metabolite from Exophiala pisciphila.
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.
Ondeyka
John G
JG
Natural Products Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA.
Zink
Deborah L
DL
Dombrowski
Anne W
AW
Polishook
Jon D
JD
Felock
Peter J
PJ
Hazuda
Daria J
DJ
Singh
Sheo B
SB
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
D001565:Benzoates; D005697:Galactosides; D019428:HIV Integrase Inhibitors; C484148:exophillic acid