Isolation, structure, and HIV-1 integrase inhibitory activity of Cytosporic acid, a fungal metabolite produced by a Cytospora sp.
HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition has the potential to lead to an anti-retroviral therapy that has advantages over existing therapies. Cytosporic acid (1) is a polyketide-derived novel natural product that was isolated from a fermentation broth of the filamentous fungus Cytospora sp. collected from Puerto Rico. It inhibited strand transfer reaction of HIV-1 integrase with an IC(50) of 20 microM. The isolation, structure elucidation, relative stereochemistry, and activity of 1 are described.
Jayasuriya
Hiranthi
H
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
Guan
Ziqiang
Z
Polishook
Jon D
JD
Dombrowski
Anne W
AW
Felock
Peter J
PJ
Hazuda
Daria J
DJ
Singh
Sheo B
SB
D004578:Electron Spin Resonance Spectroscopy; D005285:Fermentation; D005658:Fungi / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011647:Puerto Rico; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D019428:HIV Integrase Inhibitors; D013764:Tetrahydronaphthalenes; C094344:australifungin; C094345:australifunginol; C477580:cytosporic acid