Synthesis and in vitro antileishmanial activity of 5-substituted-2′-deoxyuridine derivatives

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 μM. 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 μM. Only Methia-dU (3b) was active against intramacrophagic amastigotes with an IC50 = 6.5 μM. This latter can now be evaluated in vivo, for further investigations through structure-based drug design.