Title: Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives
Authors: Pauwels, R ×
Andries, K
Desmyter, Jan
Schols, Dominique
Kukla, M J
Breslin, H J
Raeymaeckers, A
Van Gelder, Jan
Woestenborghs, R
Heykants, J #
Issue Date: Feb-1990
Series Title: Nature vol:343 issue:6257 pages:470-4
Abstract: In the search for compounds active against human immunodeficiency virus (HIV), we have found that members of a novel series of tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepine-2(1H)-one and -thione (TIBO) derivatives inhibit the replication of HIV-1, the main aetiological agent of AIDS, but not of HIV-2, or of any other DNA or RNA viruses. In five cell systems, HIV-1 is inhibited by TIBO derivatives in nanomolar amounts, which are 10(4)-10(5) times lower than the cytotoxic concentration. The unprecedented specificity of these compounds may be due to an interaction with a reverse transcriptase-associated process. By contrast, AZT (3'-azido-2',3'-dideoxythymidine), which is used for the treatment of AIDS, and DDC (2',3'-dideoxycytidine) and DDI (2',3'-dideoxyinosine), whose clinical application is being assessed, inhibit both HIV-1 and HIV-2 at concentrations that, depending on the cell systems, are 2 to 4 orders of magnitude below their cytotoxic concentration. TIBO-derivatives are new chemicals unrelated to any other antiviral agents. We believe that they are the most specific and potent inhibitors of HIV-1 replication studied so far.
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Drug Delivery and Disposition
× corresponding author
# (joint) last author

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