Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites.

Published

Journal Article

HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug strategies for anti-retroviral therapy, with potentially significant advantages over existing therapies. In this report, a series of HIV-1 inhibitors isolated from the organic extract of fermentations from terrestrial fungi is described. These fungal species, belonging to a variety of genera, were collected from throughout the world following the strict guidelines of Rio Convention on Biodiversity. The polyketide- and terpenoid-derived inhibitors are represented by two naphthoquinones, a biphenyl and two triphenyls, a benzophenone, four aromatics with or without catechol units, a linear aliphatic terpenoid, a diterpenoid, and a sesterterpenoid. These compounds inhibited the coupled and strand-transfer reaction of HIV-1 integrase with an IC(50) value of 0.5-120 micro M. The bioassay-directed isolation, structure elucidation, and HIV-1 inhibitory activity of these compounds are described.

Full Text

Duke Authors

Cited Authors

  • Singh, SB; Jayasuriya, H; Dewey, R; Polishook, JD; Dombrowski, AW; Zink, DL; Guan, Z; Collado, J; Platas, G; Pelaez, F; Felock, PJ; Hazuda, DJ

Published Date

  • December 2003

Published In

Volume / Issue

  • 30 / 12

Start / End Page

  • 721 - 731

PubMed ID

  • 14714192

Pubmed Central ID

  • 14714192

International Standard Serial Number (ISSN)

  • 1367-5435

Digital Object Identifier (DOI)

  • 10.1007/s10295-003-0101-x

Language

  • eng

Conference Location

  • Germany