Thiazolobenzimidazole: Biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor

Buckheit, Robert W.; Hollingshead, Melinda G.; Germany-Decker, Julie; White, E. Lucile; McMahon, James B.; Allen, Lois B.; Ross, L. J. N.; Decker, W. Don; Westbrook, Louise; Shannon, William M.; Weislow, Owen S.; Bader, John P.; Boyd, Michael R.

doi:10.1016/0166-3542(93)90031-d

Cited by 90 publications

(56 citation statements)

References 32 publications

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“…The importance of the choice of the template used to assess the ability of a compound to inhibit RT has also been demonstrated for diverse, nonnucleoside, HIV-1-specific RT inhibitors (7,22,24,25). As with michellamine B, compounds of that general class showed the greatest inhibition of RT activity when a heteropolymer RNA template was used.…”

Section: Discussionmentioning

confidence: 99%

Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms

McMahon

Currens

Gulakowski

et al. 1995

Antimicrob Agents Chemother

109

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Section: Discussionmentioning

confidence: 99%

Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms

McMahon

Currens

Gulakowski

et al. 1995

Antimicrob Agents Chemother

109

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“…Assays to evaluate the activity of anti-HIV compounds alone or in combination were performed utilizing the XTT measurement of virus-induced cytopathicity as described by Buckheit et al (1993).…”

Section: Antiviral Assaysmentioning

confidence: 99%

Cell-Based and Biochemical Analysis of the anti-HIV Activity of Combinations of 3′-azido-3′-deoxythymidine and Analogues of TIBO

Buckheit

White

Germany-Decker

et al. 1994

Antivir Chem Chemother

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The toxicity of 3′-azido-3′-deoxythymidine (AZT) and the appearance of drug-resistant mutants in patients treated with AZT emphasizes the critical importance of the development of alternative strategies for the therapy of AIDS patients. Combination antiviral chemotherapy provides an attractive therapeutic strategy since the dose of the individual agents may be lowered to reduce toxicity and the use of two potent antiviral agents may limit the development of drug resistance. Two analogues of tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO) potently and selectively inhibit the replication of HIV-1 in cell culture. In combination with AZT, either of the two TIBO compounds, R82913 and R86183, was highly synergistic in cell culture against HIV-1. However, in biochemical enzyme inhibition assays, utilizing recombinant HIV-1 reverse transcriptase, synergy was not detected at the enzymatic level. These results suggest that one of these two known inhibitors of HIV-1 reverse transcriptase may have a secondary mechanism of action distinct from inhibition of the reverse transcriptase.

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“…It was found to act as a specific HIV-1 RT inhibitor, and proved inactive against the pyridinone-resistant virus strain A17. Furthermore TBZ in combination with either AZT or ddI synergistically inhibited HIV-1-induced cytopathicity in vitro (Buckheit et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…1992; Buckheit et al, 1993;El Dareer et al, 1993;Hizi et al, 1993;Tinwalla et al, 1993) and it proved to be a nonnucleoside RT inhibitor (NNRTI). TBZ was found to be active against a panel ofbiologically diverse laboratory and 'clinical strains of HIV-1 including the AZT-resistant strain G910-6.…”

Section: Introductionmentioning

confidence: 99%

Structural Features and Anti-Human Immunodeficiency Virus (HIV) Activity of the Isomers of 1-(2′,6′-Difluorophenyl)-1H,3H-Thiazolo[3,4-a]Benzimidazole, a Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitor

Chimirri

Grasso

Molica

et al. 1997

Antivir Chem Chemother

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The structural features, including the absolute configuration, of the enantiomers of 1-(2′,6′-difluorophenyl)-1 H,3 H-thiazolo[3,4- a]benzimidazole (TBZ; NSC 625487), the lead compound of a new class of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitors (NNRTIs), are described. Diffractometric analysis revealed that TBZ, like other NNRTIs, assumes a butterfly-like conformation in which the phenyl ring at C1 is in an orthogonal orientation relative to the thiazolobenzimidazole system, and the 2′,6′-fluorine atoms form two intramolecular hydrogen bonds with H1 and one of the methylene protons at C3, respectively. The stereochemistry in solution, as confirmed by lanthanide shift reagent-assisted ‘H NMR, paralleled the situation present in the solid state. The in vitro anti-HIV activity of the two enantiomers was also evaluated and the results obtained showed that the R-(+) is more active than the S-(−) isomer in inhibiting HIV-1 replication. Resistance and cross-resistance to other NNRTIs as well as inhibitory effects on HIV-1 reverse transcriptase activity are also reported.

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Thiazolobenzimidazole: Biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor

Cited by 90 publications

References 32 publications

Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms

Michellamine B, a novel plant alkaloid, inhibits human immunodeficiency virus-induced cell killing by at least two distinct mechanisms

Cell-Based and Biochemical Analysis of the anti-HIV Activity of Combinations of 3′-azido-3′-deoxythymidine and Analogues of TIBO

Structural Features and Anti-Human Immunodeficiency Virus (HIV) Activity of the Isomers of 1-(2′,6′-Difluorophenyl)-1H,3H-Thiazolo[3,4-a]Benzimidazole, a Potent Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitor

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