In vitro effects of purine and pyrimidine analogues on Leishmania donovani and Leishmania infantum promastigotes and intracellular amastigotes

Abstract : Inhibition of parasite metabolic pathways is a rationale for new chemotherapeutic strategies. The pyrimidine and purine salvage pathways are thus targets against Leishmania donovani and L. infantum, causative agents of visceral human leishmaniasis and canine leishmaniosis. The antiproliferative effect of the pyrimidine analogues Cytarabine and 5-fluorouracil and of the purine analogues Azathioprine and 6-mercaptopurine was evaluated in vitro on the promastigote and the intracellular amastigote stages of the parasite. Cytarabine and 5-fluorouracil were the best inhibitors against promastigotes, whereas 5- fluorouracil and azathioprine displayed the best efficacy against the amastigote stage. The ultrastructural study showed an important cytoplasmic vacuolization and with azathioprine and 5-fluorouracyl, a mitochondrial swelling and appearance of autophagosome-like structures. Alterations of the kinetoplast were also observed with 5-fluorouracil, all these damages eventually resulting in an autolysis process that triggered the subsequent death of the intracellular parasites.
Document type :
Journal articles
Complete list of metadatas

Cited literature [21 references]  Display  Hide  Download

https://hal-univ-lyon1.archives-ouvertes.fr/hal-02111046
Contributor : Philippe Lawton <>
Submitted on : Friday, April 26, 2019 - 8:23:58 AM
Last modification on : Saturday, April 27, 2019 - 1:26:37 AM

File

22-Azzouz & Lawton 17.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Philippe Lawton, Samira Azzouz. In vitro effects of purine and pyrimidine analogues on Leishmania donovani and Leishmania infantum promastigotes and intracellular amastigotes. Acta Parasitologica, Springer Verlag, 2017, 62 (3), pp.582-588. ⟨10.1515/ap-2017-0070⟩. ⟨hal-02111046⟩

Share

Metrics

Record views

49

Files downloads

51