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Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside ?-triphosphates.

ABSTRACT: 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 ?-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 ?-triphosphate (1) and AZT ?-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 10nM, 10 and 100 ?M, respectively.

SUBMITTER: Dash C

PROVIDER: S-EPMC3114884 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates.

Dash Chandravanu C Ahmadibeni Yousef Y Hanley Michael J MJ Pandhare Jui J Gotte Mathias M Le Grice Stuart F J SF Parang Keykavous K

Bioorganic & medicinal chemistry letters 20110508 12

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 (d ...[more]

PMID: 21605974

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