Abstract |
Thiazolobenzimidazole ( NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity.
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Authors | R W Buckheit Jr, M G Hollingshead, J Germany-Decker, E L White, J B McMahon, L B Allen, L J Ross, W D Decker, L Westbrook, W M Shannon |
Journal | Antiviral research
(Antiviral Res)
Vol. 21
Issue 3
Pg. 247-65
(Jul 1993)
ISSN: 0166-3542 [Print] Netherlands |
PMID | 7692815
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antiviral Agents
- Benzimidazoles
- DNA, Single-Stranded
- Reverse Transcriptase Inhibitors
- Thiazoles
- 1-(2',6'-difluorophenyl)-1H,3H-thiazolo(3,4-a)benzimidazole
- Zidovudine
- HIV Reverse Transcriptase
- Didanosine
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Topics |
- Antiviral Agents
(pharmacology)
- Base Sequence
- Benzimidazoles
(pharmacology)
- Cell Line
- DNA, Single-Stranded
- Didanosine
(pharmacology)
- Drug Synergism
- HIV Reverse Transcriptase
- HIV-1
(drug effects, enzymology)
- Humans
- Leukemia Virus, Murine
(drug effects)
- Molecular Sequence Data
- Molecular Structure
- Reverse Transcriptase Inhibitors
- Thiazoles
(pharmacology)
- Zidovudine
(pharmacology)
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