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JAC Advance Access published online on January 13, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh530
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JAC © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved

Leading article

Pyridine N-oxide derivatives: unusual anti-HIV compounds with multiple mechanisms of antiviral action

Jan Balzarini 1*, Miguel Stevens 1, Erik De Clercq 1, Dominique Schols 1, and Christophe Pannecouque 1

1 Rega Institute for Medical Research, K. U. Leuven, B-3000 Leuven, Belgium

* To whom correspondence should be addressed.
Jan Balzarini, E-mail: jan.balzarini{at}rega.kuleuven.ac.be


  Abstract

Pyridine N-oxide derivatives represent a new class of anti-HIV compounds, for which some members exclusively act through inhibition of HIV-1 reverse transcriptase and thus characteristically behave as non-nucleoside reverse transcriptase inhibitors. Other members act, additionally or alternatively, at a post-integrational event in the replication cycle of HIV, that is, at the level of HIV gene expression. Repeated administration of one of the prototype compounds (JPL-32) to DBA/2 and hu-PBMC-SCID mice demonstrated, in the absence of any acute toxicity, protective activity against HIV-induced destruction of CD4 human T lymphocytes.

Keywords: NF-{kappa}B; reverse transcriptase; NNRTI;transcription inhibitors; HIV chemotherapy.
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