title: The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment.
abstract: Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes.
authors.affiliation: a Omnia Molecular S.L. , Barcelona , Spain.
authors.forename: Adélaïde
authors.initials: A
authors.lastname: Saint-Léger
authors.affiliation: a Omnia Molecular S.L. , Barcelona , Spain.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sinadinos
authors.affiliation: a Omnia Molecular S.L. , Barcelona , Spain.|b Institute for Research in Biomedicine (IRB Barcelona) , Barcelona , Spain.|c Catalan Institution for Research and Advanced Studies (ICREA) , Barcelona , Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Ribas de Pouplana
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism*; D000962:Antimalarials / Q000494:pharmacology; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D016778:Malaria, Falciparum / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000201:enzymology*
chemical_list: D000962:Antimalarials; D000604:Amino Acyl-tRNA Synthetases
keywords: Aminoacyl-tRNA synthetase; Plasmodium falciparum; borrelidin; cladosporin; halofuginone; malaria