title: Integracides: tetracyclic triterpenoid inhibitors of HIV-1 integrase produced by Fusarium sp.
abstract: HIV-1 integrase is a critical enzyme in the replication of HIV-1. It is absent in the host cells and therefore is a good target for treatment of HIV-1 infections. Integracides are members of the tetracyclic triterpenoids family that were isolated from the fermentation broth of a Fusarium sp. Integracide A, a sulfated ester, exhibited significant inhibitory activity against strand transfer reaction of HIV-1 integrase. The discovery, structure elucidation including single crystal X-ray structure and HIV-1 inhibitory activity of these compounds are described.
authors.affiliation: Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. sheo_singh@merck.com
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
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: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Jorden
authors.initials: J
authors.lastname: Hirshfield
authors.forename: Peter
authors.initials: P
authors.lastname: Felock
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
mesh_terms: D018360:Crystallography, X-Ray; D005285:Fermentation; D005670:Fusarium / Q000378:metabolism*; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D014315:Triterpenes; D019427:HIV Integrase