Synthesis and Anti-HIV Activity of a Series of 6-Modified 2′,3′-Dideoxyguanosine and 2′,3′-Didehydro-2′,3′-dideoxyguanosine Analogs

Authors

  • Lujia Xie,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Xiantao Yang,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Delin Pan,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Yingli Cao,

    1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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  • Mou Cao,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Guichun Lin,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Zhu Guan,

    Corresponding author
    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
    • State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Ying Guo,

    1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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  • Lihe Zhang,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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  • Zhenjun Yang

    Corresponding author
    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
    • State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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Abstract

In search of potential 2′,3′-dideoxyguanosine (ddG) and 2′,3′-didehydro-2′,3′-dideoxyguanosine (D4G) prodrugs, a series of 6-modified ddG, D4G analogs were synthesized and evaluated for their anti-HIV activities and cytotoxities in cell-based assays. All analogs showed low cytotoxicities and some of them displayed benign anti-HIV activities. The active triphosphate forms in vivo, ddGTP and D4TTP, were also synthesized by a novel and facile "one-pot" method. The recognition of ddGTP and D4TTP by Taq, Therminater DNA polymerase and HIV reverse transcriptase (RT) incorporated in DNA/RNA strands were investigated by a non-radioactivity method and Km were determined.

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