Date of Original Version
Biomedical and Pharmaceutical Sciences
Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 nM, 10 and 100 μM, respectively.
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Dash, C., Ahmadibeni, Y., Hanley, M. J., Pandhare, J., Gotte, M., Le Grice, S. F.J., & Parang, K. (2011). Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates. Bioorganic & Medicinal Chemistry Letters, 21(12), 3519-3522. doi: 10.1016/j.bmcl.2011.05.005
Available at: https://doi.org/10.1016/j.bmcl.2011.05.005
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