| Literature DB >> 21700368 |
Hong-Wang Zhang1, Mervi Detorio, Brian D Herman, Sarah Solomon, Leda Bassit, James H Nettles, Aleksandr Obikhod, Si-Jia Tao, John W Mellors, Nicolas Sluis-Cremer, Steven J Coats, Raymond F Schinazi.
Abstract
Microwave-assisted optimized transglycosylation reactions were used to prepare eleven modified l-3'-azido-2',3'-dideoxypurine nucleosides. These l-nucleoside analogs were evaluated against HIV and hepatitis B virus. The l-3'-azido-2',3'-dideoxypurines nucleosides were metabolized to nucleoside 5'-triphosphates in primary human lymphocytes, but exhibited weak or no antiviral activity against HIV-1. The nucleosides were also inactive against HBV in HepG2 cells. Pre-steady state kinetic experiments demonstrated that the l-3'-azido-2',3'-dideoxypurine triphosphates could be incorporated by purified HIV-1 reverse transcriptase, although their catalytic efficiency (k(pol)/K(d)) of incorporation was low. Interestingly, a phosphoramidate prodrug of l-3'-azido-2',3'-dideoxyadenosine exhibited anti-HIV-1 activity without significant toxicity. Published by Elsevier Masson SAS.Entities:
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Year: 2011 PMID： 21700368 PMCID： PMC3242641 DOI： 10.1016/j.ejmech.2011.05.051
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514