Current status and progresses made in malaria chemotherapy.
Malaria is the most important parasitic disease worldwide, affecting more than 500 million people and causing close to 1 million deaths per annum. This serious fact is mainly attributable to the emergence of drug resistant strains of Plasmodium falciparum. The advances made in malaria chemotherapy based on unique aspects of the biochemistry and physiology of the responsible agents for this disease, parasites of Plasmodium genus, are covered in this review. Increasing resistance to conventional antimalarial drugs constitutes the main drawback for the persistence of this disease. In the present article, a comprehensive analysis of selected molecular targets is depicted in terms of their potential utility as chemotherapeutic agents. Our review focuses on different and important molecular targets for drug design that include proteases that hydrolyze hemoglobin, protein farnesyltransferase, heme detoxification pathway, polyamine pathways, dihydrofolate reductase, artemisinin-based combination therapies (ACTs), etc. Therefore, rational approaches to control malaria targeting metabolic pathways of malaria parasites which are essential for parasites survival are presented.
Liñares
Guadalupe E García
GE
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
Rodriguez
Juan B
JB
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use; D003546:Cysteine Endopeptidases / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D004351:Drug Resistance; D005227:Fatty Acids / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors; D006420:Hemeproteins / Q000187:drug effects; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000502:physiology; D011073:Polyamines / Q000378:metabolism; D012717:Sesquiterpenes / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013879:Thioredoxins / Q000378:metabolism
D000962:Antimalarials; D037621:Artemisinins; D015853:Cysteine Proteinase Inhibitors; D005227:Fatty Acids; D006420:Hemeproteins; D011073:Polyamines; D012717:Sesquiterpenes; C020753:hemozoin; D013879:Thioredoxins; C031327:artemisinin; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D005982:Glutathione Transferase; D003546:Cysteine Endopeptidases; C099607:falcipain; D005978:Glutathione