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5'-Trityl-substituted thymidine derivatives as a novel class of antileishmanial agents: Leishmania infantum EndoG as a potential target

AuthorsCasanova, 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
Keywordsamino acids
trityl groups
Issue Date2013
PublisherJohn Wiley & Sons
CitationChemMedChem (2013)
AbstractTwo 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.
Publisher version (URL)http://dx.doi.org/10.1002/cmdc.201300129
Appears in Collections:(IQM) Artículos
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