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  • Title: Synthesis and in vitro antileishmanial activity of 5-substituted-2'-deoxyuridine derivatives.
    Author: Peyron C, Benhida R, Bories C, Loiseau PM.
    Journal: Bioorg Chem; 2005 Dec; 33(6):439-47. PubMed ID: 16168460.
    Abstract:
    We report herein the synthesis and the in vitro antileishmanial evaluation of 5-substituted-2'-deoxyuridine nucleosides. The most active compound against Leishmania donovani promastigotes was Thia-dU (3a) with an IC50 =3 microM. This compound exhibited the same activity as zidovudine (3'-azido-2'-deoxythymidine) used as nucleoside reference compound. Considering the cytotoxicity of synthetic compounds on peritoneal murine macrophages, the most toxic compound was MeThio-dU (3d) with a MTC at 10 microM. Only Methia-dU (3b) was active against intramacrophagic amastigotes with an IC50 =6.5 microM. This latter can now be evaluated in vivo, for further investigations through structure-based drug design.
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