NEW YORK (Reuters Health) - Pyridine oxide derivatives not only have the ability to inhibit HIV replication in cell culture, they also interfere with viral gene expression, according to the latest research from a team that has been studying these novel compounds.
Previously, Dr. Jan Balzarini, Dr. Miguel Stevens, and others from the Rega Institute for Medical Research in Leuven, Belgium found that several pyridine oxide derivatives selectively target HIV-1 reverse transcriptase (RT), acting much like the non-nucleoside reverse transcriptase inhibitors (NNRTIs). (See Reuters Health report Sep. 24, 2003). “This target is operative before the incorporation of the viral genome in the host cell chromosomes,” Dr. Balzarini said.
“But several [other] members of this group of compounds have clearly an inhibitory effect against HIV at a target in the replication cycle of the virus that is operational after the virus is incorporated in the host cell chromosomes,” she continued.
These compounds inhibit both HIV-1 and HIV-2 RT and are the focus of the team’s latest work, published in the October issue of Antimicrobial Agents and Chemotherapy.
In contrast to the pyridine oxides that inhibit just HIV-1, those that inhibit both HIV-1 and HIV-2 possess a novel dual mode of anti-HIV action independent from HIV RT inhibition, Dr. Balzarini and colleagues report.
“Time-of-addition experiments revealed that these pyridine oxide derivatives interact at a postintegration step in the replication cycle of HIV,” they write. “The compounds interfere with the transcription process (converting the proviral DNA to RNA) and may have the potential to prevent reactivation of the virus, which is an interesting added value for the compounds,” Dr. Balzarini said.
“This unique feature, as well as the wealth of chemical modifications that may be introduced into this series of molecules, makes this class of compounds of potential interest as a new lead in the development of candidate drugs for anti-HIV chemotherapy,” the researchers write.
Source: Antimicrob Agents Chemother 2003;47:3109-3116. [ Google search on this article ]
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