101. 5'-Trityl-substituted thymidine derivatives as a novel class of antileishmanial agents: Leishmania infantum EndoG as a potential target
- Author
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Comisión Interministerial de Ciencia y Tecnología, CICYT (España), Consejo Superior de Investigaciones Científicas (España), Comunidad de Madrid, Junta de Comunidades de Castilla-La Mancha, Casanova, Elena, Moreno, David, Gigante, Alba, Genes, Carlos Mario, Rico, Eva, Oliva, Cristina, Camarasa Rius, María José, Gago, Federico, Jiménez-Ruiz, Antonio, Peréz-Pérez, María-Jesús, Comisión Interministerial de Ciencia y Tecnología, CICYT (España), Consejo Superior de Investigaciones Científicas (España), Comunidad de Madrid, Junta de Comunidades de Castilla-La Mancha, Casanova, Elena, Moreno, David, Gigante, Alba, Genes, Carlos Mario, Rico, Eva, Oliva, Cristina, Camarasa Rius, María José, Gago, Federico, Jiménez-Ruiz, Antonio, and Peréz-Pérez, María-Jesús
- Abstract
Two series of 5’-triphenylmethyl (trityl)-substituted thymidine derivatives were synthesized and tested against Leishmania infantum axenic promastigotes and amastigotes. Several of these compounds show significant antileishmanial activity, with IC50 values in the low micromolar range. Among these, 3’-O-(isoleucylisoleucyl)- 5’-O-(3,3,3-triphenylpropanoyl)thymidine displays particularly good activity against intracellular amastigotes. Assays performed to characterize the nature of parasite cell death in the presence of the tritylthymidines indicated significant alterations in mitochondrial transmembrane potential, an increase in superoxide concentrations, and also significant decreases in DNA degradation during the cell death process. Results point to the mitochondrial nuclease LiEndoG as a target for the action of this family of compounds.
- Published
- 2013