Isolation, structure, and HIV-1 integrase inhibitory activity of Cytosporic acid, a fungal metabolite produced by a Cytospora sp

Hiranthi Jayasuriya; Ziqiang Guan; Jon D Polishook; Anne W Dombrowski; Peter J Felock; Daria J Hazuda; Sheo B Singh

doi:10.1021/np020533g

Isolation, structure, and HIV-1 integrase inhibitory activity of Cytosporic acid, a fungal metabolite produced by a Cytospora sp

J Nat Prod. 2003 Apr;66(4):551-3. doi: 10.1021/np020533g.

Authors

Hiranthi Jayasuriya¹, Ziqiang Guan, Jon D Polishook, Anne W Dombrowski, Peter J Felock, Daria J Hazuda, Sheo B Singh

Affiliation

¹ Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.

PMID: 12713414
DOI: 10.1021/np020533g

Abstract

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.

MeSH terms

Electron Spin Resonance Spectroscopy
Fermentation
Fungi / chemistry*
HIV Integrase Inhibitors / chemistry
HIV Integrase Inhibitors / isolation & purification*
HIV Integrase Inhibitors / pharmacology
HIV-1 / enzymology*
Inhibitory Concentration 50
Molecular Structure
Puerto Rico
Stereoisomerism
Tetrahydronaphthalenes / chemistry
Tetrahydronaphthalenes / isolation & purification*
Tetrahydronaphthalenes / pharmacology

Substances

HIV Integrase Inhibitors
Tetrahydronaphthalenes
australifungin
australifunginol
cytosporic acid