Synthesis and Evaluation of Novel Ether Lipid Nucleoside Conjugates for Anti-HIV-1 Activity

Claude Piantadosi, Canio J. Marasco, Susan L. Morris-Natschke, Karen L. Meyer, Fatma Gumus, Jefferson R. Surles, Khalid S. Ishaq, Louis S. Kucera, Nathan Iyer, C. Anne Wallen, Steven Piantadosi, Edward J. Modest

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Combinations of an amidoalkylphosphocholine, 8, and AZT have been found to cause an apparent synergistic action in suppressing infectious HIV-1 replication. In addition, amidoalkyl, oxyalkyl, and thioalkyl ether lipids have been chemically linked to anti-HIV-1 nucleosides (AZT and DDI) through phosphate and phosphonate linkages. These conjugates have shown promising in vitro anti-HIV-1 activity. Also, the conjugates have a 5-10-fold reduction in cell cytotoxicity compared to AZT alone. The most active compound, an amidoalkyl ether lipid-AZT conjugate, 4A, was found to have a differential selectivity of 1793 in a syncytial plaque assay. In comparison, AZT alone has a value of 1281.

    Original languageEnglish (US)
    Pages (from-to)1408-1414
    Number of pages7
    JournalJournal of medicinal chemistry
    Volume34
    Issue number4
    DOIs
    StatePublished - Apr 1 1991

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

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