Isolation, Structure and HIV-1 Integrase Inhibitory Activity of Exophillic Acid,
a Novel Fungal Metabolite from Exophiala pisciphila

JOHN G. ONDEYKA,^† DEBORAH L. ZINK,^† ANNE W. DOMBROWSKI,^† JON D. POLISHOOK,^†
PETER J. FELOCK,^†† DARIA J. HAZUDA^†† and SHEO B. SINGH^†,*

^† Natural Products Chemistry, Merck Research Laboratories,
P. O. Box 2000, Rahway, New Jersey 07065 (USA)
^†† Department of Antiviral Research, Merck Research Laboratories,
West Point, Pennsylvania 19486 (USA)

(Received for publication September 26, 2003)

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 μM, respectively.