2024-03-29T00:15:34Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/784762020-05-27T12:19:24Zcom_10261_81com_10261_5col_10261_334
urn:hdl:10261/78476
5'-Trityl-substituted thymidine derivatives as a novel class of antileishmanial agents: Leishmania infantum EndoG as a potential target
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
Amino acids
endonucleases
Leishmania
thymidine
trityl groups
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.
2013
artículo
ChemMedChem (2013)
1860-7179
http://hdl.handle.net/10261/78476
10.1002/cmdc.201300129
1860-7187
http://dx.doi.org/10.13039/501100007273
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/100012818
http://dx.doi.org/10.13039/501100011698
eng
http://dx.doi.org/10.1002/cmdc.201300129
closedAccess
John Wiley & Sons