Pyridine N-oxide derivatives: unusual anti-HIV compounds with multiple mechanisms of antiviral action.
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.
Balzarini
Jan
J
Rega Institute for Medical Research, K. U. Leuven, B-3000 Leuven, Belgium. jan.balzarini@rega.kuleuven.ac.be
Stevens
Miguel
M
De Clercq
Erik
E
Schols
Dominique
D
Pannecouque
Christophe
C
D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D011725:Pyridines; C013229:pyridine N-oxide