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[摘要]：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 beta-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 beta-triphosphate (1) and AZT beta-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 mu M, respectively. (C) 2011 Elsevier Ltd. All rights reserved. |
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