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Novel human immunodeficiency virus (HIV) inhibitors that have a dual mode of anti-HIV action.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2003 Oct; Vol. 47 (10), pp. 3109-16. - Publication Year :
- 2003
-
Abstract
- We have found that novel pyridine oxide derivatives are inhibitors of a wide range of human immunodeficiency virus (HIV) type 1 (HIV-1) and HIV-2 strains in CEM cell cultures. Some of the compounds showed inhibitory activities against recombinant HIV-1 reverse transcriptase (RT), whereas others were totally inactive against this viral protein in vitro. Partial retention of anti-HIV-1 activity against virus strains that contain a variety of mutations characteristic of those for resistance to nonnucleoside RT inhibitors and a lack of inhibitory activity against recombinant HIV-2 RT suggested that these pyridine oxide derivatives possess a mode of antiviral action independent from HIV RT inhibition. Time-of-addition experiments revealed that these pyridine oxide derivatives interact at a postintegration step in the replication cycle of HIV. Furthermore, it was shown that these compounds are active not only in acutely HIV-1-infected cells but also in chronically HIV-infected cells. A dose-dependent inhibition of virus particle release and viral protein expression was observed upon exposure to the pyridine oxide derivatives. Finally, inhibition of HIV-1 long terminal repeat-mediated green fluorescence protein expression in quantitative transactivation bioassays indicated that the additional target of action of the pyridine oxide derivatives may be located at the level of HIV gene expression.
- Subjects :
- Amino Acid Substitution
Cell Line
Cell Survival drug effects
Dose-Response Relationship, Drug
Gene Expression Regulation, Viral drug effects
Green Fluorescent Proteins
HIV enzymology
HIV genetics
HIV physiology
HIV Reverse Transcriptase antagonists & inhibitors
HIV Reverse Transcriptase genetics
HeLa Cells
Humans
Luminescent Proteins biosynthesis
Luminescent Proteins genetics
Microbial Sensitivity Tests
Pyridinium Compounds chemistry
Recombinant Proteins antagonists & inhibitors
Viral Proteins biosynthesis
Virus Replication drug effects
Virus Replication physiology
Anti-HIV Agents pharmacology
HIV drug effects
Pyridinium Compounds pharmacology
Reverse Transcriptase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 47
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 14506017
- Full Text :
- https://doi.org/10.1128/AAC.47.10.3109-3116.2003