Integracides: tetracyclic triterpenoid inhibitors of HIV-1 integrase produced by Fusarium sp.
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.
Singh
Sheo B
SB
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. sheo_singh@merck.com
Zink
Deborah L
DL
Dombrowski
Anne W
AW
Polishook
Jon D
JD
Ondeyka
John G
JG
Hirshfield
Jorden
J
Felock
Peter
P
Hazuda
Daria J
DJ
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*
D019428:HIV Integrase Inhibitors; D014315:Triterpenes; D019427:HIV Integrase