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

Chandravanu Dash, Yousef Ahmadibeni, Michael J. Hanley, Jui Pandhare, Mathias Gotte, Stuart F J Le Grice, Keykavous Parang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3519-3522
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number12
StatePublished - Jun 15 2011
Externally publishedYes


  • DNA polymerase
  • HIV
  • Multi-drug resistant
  • Nucleoside
  • Reverse transcriptase
  • Solid-phase synthesis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry


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