Synthesis and in vitro antileishmanial activity of 5-substituted-2'-deoxyuridine derivatives. 2005

Corinne Peyron, and Rachid Benhida, and Christian Bories, and Philippe M Loiseau
Laboratoire de Chimie Bioorganique UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose F-06108, Nice Cédex 2, France.

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.

UI MeSH Term Description Entries
D007893 Leishmania donovani A parasitic hemoflagellate of the subgenus Leishmania leishmania that infects man and animals and causes visceral leishmaniasis (LEISHMANIASIS, VISCERAL). The sandfly genera Phlebotomus and Lutzomyia are the vectors. Leishmania (Leishmania) donovani,Leishmania leishmania donovani,Leishmania donovanus,Leishmania leishmania donovanus,donovani, Leishmania leishmania,donovanus, Leishmania,donovanus, Leishmania leishmania,leishmania donovanus, Leishmania
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D003857 Deoxyuridine 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. (beta 1-(2-Deoxyribopyranosyl))thymidine
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000981 Antiprotozoal Agents Substances that are destructive to protozoans. Schizonticides,Agents, Antiprotozoal
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D017737 Macrophages, Peritoneal Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum. Peritoneal Macrophages,Macrophage, Peritoneal,Peritoneal Macrophage
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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