title: Isolation, structure, absolute stereochemistry, and HIV-1 integrase inhibitory activity of integrasone, a novel fungal polyketide.
abstract: HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug targets for anti-retroviral therapy with potentially significant advantages over existing therapies. In this Note, the isolation, structure elucidation, and absolute stereochemistry of integrasone, a novel polyketide, derived from an unidentified sterile mycelium have been described. This bicyclic dihydroxy epoxide lactone inhibited the strand transfer reaction of HIV-1 integrase with an IC(50) of 41 microM.
authors.affiliation: Natural Products Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: Kithsiri B
authors.initials: KB
authors.lastname: Herath
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.forename: Jon D
authors.initials: JD
authors.lastname: Polishook
authors.forename: Anne W
authors.initials: AW
authors.lastname: Dombrowski
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
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: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D005658:Fungi / Q000737:chemistry*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005663:Furans; D019428:HIV Integrase Inhibitors; C487245:integrasone; D019427:HIV Integrase