Thiated derivatives of 2′,3′-dideoxy-3′-fluorothymidine: Synthesis, in vitro anti-HIV-1 activity and interaction with recombinant drug resistant HIV-1 reverse transcriptase forms

被引：3
|
作者：
Miazga, Agnieszka [1 ]
Hamy, Francois [2 ]
Louvel, Severine [2 ]
Klimkait, Thomas [2 ]
Pietrusiewicz, Zofia [3 ]
Kurzynska-Kokorniak, Anna [3 ]
Figlerowicz, Marek [3 ]
Winska, Patrycja [1 ]
Kulikowski, Tadeusz [1 ]
机构：
[1] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland
[2] InPheno AG, CH-4051 Basel, Switzerland
[3] Polish Acad Sci, Inst Bioorgan Chem, PL-61704 Poznan, Poland
来源：
ANTIVIRAL RESEARCH | 2011年 / 92卷 / 01期
关键词：
Anti HIV-1 agents; NRTI; HIV-1; mutants; NUCLEOSIDE ANALOGS; DNA; INHIBITION; 3'-FLUOROTHYMIDINE; 5'-TRIPHOSPHATES; PHOSPHORYLATION; TRIPHOSPHATE; TOXICITY; CELLS;
D O I：
10.1016/j.antiviral.2011.05.012
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Various thiated analogues of thymine 2',3'-dideoxy-3'-fluoronucleoside (FLT) and their 5'-monophosphates and 5'-triphosphates were prepared with the use of modified multistep procedures. The thiated analogues of FLT and FLTMP were evaluated against the wild type and drug- and multidrug-resistant strains of HIV-1, using the replicative phenotyping format of the deCIPhR assay, and showed potent inhibition of drug-resistant HIV-1 strains at low cytotoxicity. Additionally, inhibition of recombinant drug resistant forms of reverse transcriptase from single and multiple HIV-1 mutants by the synthesized 5'-triphosphates was investigated. The strongest inhibition was observed for K103N and Delta 67 mutants and the most potent anti-HIV-1 activity against drug resistant strains and the lowest cytotoxicity was exerted by S(4)FLTMP and FLTMP which may be regarded as potential anti-HIV/AIDS agents. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码：57 / 63
页数：7
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