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7075448 
Journal Article 
Review 
New Molecular Targets and Strategies for Antimalarial Discovery 
Aguiar, AC; de Sousa, LRF; Garcia, CRS; Oliva, G; Guido, RVC; , 
2019 
Yes 
Current Medicinal Chemistry
ISSN: 0929-8673
EISSN: 1875-533X 
BENTHAM SCIENCE PUBL LTD 
SHARJAH 
26 
23 
4380-4402 
English 
28875841 
WOS:000489555700005 
Malaria remains a major health problem, especially because of the emergence of resistant P. falciparum strains to artemisinin derivatives. In this context, safe and affordable antimalarial drugs are desperately needed. New proteins have been investigated as molecular targets for research and development of innovative compounds with well-defined mechanism of action. In this review, we highlight genetically and clinically validated plasmodial proteins as drug targets for the next generation of therapeutics. The enzymes described herein are involved in hemoglobin hydrolysis, the invasion process, elongation factors for protein synthesis, pyrimidine biosynthesis, post-translational modifications such as prenylation, phosphorylation and histone acetylation, generation of ATP in mitochondrial metabolism and aminoacylation of RNAs. Significant advances on proteomics, genetics, structural biology, computational and biophysical methods provided invaluable molecular and structural information about these drug targets. Based on this, several strategies and models have been applied to identify and improve lead compounds. This review presents the recent progresses in the discovery of antimalarial drug candidates, highlighting the approaches, challenges, and perspectives to deliver affordable, safe and low single-dose medicines to treat malaria.