Inhibition of Multi-Drug Resistant HIV-1 Reverse Transcriptase by Nucleoside Beta-Triphosphates

Authors

Chandravanu Dash, Meharry Med CollegeFollow
Yousef Ahmadibeni, Columbus State UniversityFollow
Michael J. Hanley, University of Rhode Island
Jui Pandhare, Meharry Med College
Mathias Gotte, McGill University
Stuart F. J. Le Grice, National Cancer InstituteFollow
Keykavous Parang, Chapman UniversityFollow

Document Type

Article

Publication Date

2011

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 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.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters, volume 21, issue 12, in 2011. DOI: 10.1016/j.bmcl.2011.05.005

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Recommended Citation

Dash, Chandravanu, Yousef Ahmadibeni, Michael J. Hanley, Jui Pandhare, Mathias Gotte, Stuart FJ Le Grice, and Keykavous Parang. "Inhibition of multi-drug resistant HIV-1 reverse transcriptase by nucleoside β-triphosphates." Bioorganic & medicinal chemistry letters 21, no. 12 (2011): 3519-3522.
DOI: 10.1016/j.bmcl.2011.05.005

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.