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  • Title: Synthesis, biological properties and anti-HIV-1 activity of new pyrimidine P1,P2-dinucleotides.
    Author: Miazga A, Ziemkowski P, Siwecka MA, Lipniacki A, Piasek A, Kulikowski T.
    Journal: Nucleosides Nucleotides Nucleic Acids; 2010 Jun; 29(4-6):438-44. PubMed ID: 20544533.
    Abstract:
    New homo- and hetero-P(1),P(2)-dinucleotides were prepared with the use of multistep procedures starting from the monophosphates of 3'-fluoro-2-thiothymidine, 3'-fluoro-4-thiothymidine, AZT and 1-[(2-hydroxyethoxy)-methyl-5-propyl-6-phenylselenenyl]uracil. Anti-HIV properties of the synthesized P(1),P(2)-dinucleotides were evaluated against laboratory syncytia inducing strain HIV-1 in CEM-T4 cells. Anti-HIV activities were in the range of 5-45 nM, and therapeutic indexes were higher than 4666-14000. Interactions of the above mentioned compounds with recombinant HIV-1 reverse transcriptase were also investigated. The obtained results point to reverse transcriptase inhibition, with somewhat lower inhibitory activity than that of their parental nucleoside-5'-triphosphates. Compound 6 may be regarded as a potent anti-HIV/AIDS drug.
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