Plasmodium Purine Metabolism and Its Inhibition by Nucleoside and Nucleotide Analogues.

J Med Chem

Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 UM-CNRS-ENSCM , Université Montpellier, Equipe Nucléosides & Effecteurs Phosphorylés , Place E. Bataillon, cc 1704 , 34095 Montpellier , France.

Published: September 2019

Malaria still affects around 200 million people and is responsible for more than 400,000 deaths per year, mostly children in subequatorial areas. This disease is caused by parasites of the genus. Only a few WHO-recommended treatments are available to prevent or cure plasmodial infections, but genetic mutations in the causal parasites have led to onset of resistance against all commercial antimalarial drugs. New drugs and targets are being investigated to cope with this emerging problem, including enzymes belonging to the main metabolic pathways, while nucleoside and nucleotide analogues are also a promising class of potential drugs. This review highlights the main metabolic pathways targeted for the development of potential antiplasmodial therapies based on nucleos(t)ide analogues, as well as the different series of purine-containing nucleoside and nucleotide derivatives designed to inhibit purine metabolism.

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http://dx.doi.org/10.1021/acs.jmedchem.9b00182DOI Listing

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