Effects of selected purine and pyrimidine inhibitors on Leishmania donovani and L. infantum in vitro

What is it about?

Interference with parasite metabolisms has been a chemotherapeutic target since a number of years. However, very few recently published material is related to the in vitro effect of purine and pyrimidine derivatives on Leishmania parasites, especially when it comes to ultrastructural alteration of intracellular visceral leishmaniosis parasites. We focused on selected analogues and showed that their effects were different according to the parasites’ stages and that ultrastructural alterations of the intra-macrophagic parasites triggered an autolysis process.

Featured Image

Why is it important?

The first-line therapies against visceral leishmaniasis require parenteral administration, they have significant toxic side effects and widespread resistance to them has been reported. A rational discovery of novel antiparasitic drugs should be based on parasite-specific metabolisms. Pyrimidine biosynthesis is a vital biological process and like most parasitic protozoa, Leishmania is also an obligate purine auxotroph and hence depends on its own purine salvage pathway that has also been considered as a target for novel treatments against leishmaniasis.In the present work, we tested drugs used against other diseases in humans, two purine analogues – 6-mercaptopurine and azathioprine – and two pyrimidine derivatives – cytarabine and 5-fluorouracil – on the promastigote and amastigote stages of L. donovani and L. infantum, two agents of visceral diseases that exhibit a clinical polymorphism.