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 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.
Peyron
Corinne
C
Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose F-06108, Nice Cédex 2, France.
Benhida
Rachid
R
Bories
Christian
C
Loiseau
Philippe M
PM
D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003857:Deoxyuridine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D003857:Deoxyuridine