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Abstract:

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. © 2007 Bentham Science Publishers Ltd.

Registro:

Documento: Artículo
Título:Current status and progress made in malaria chemotherapy
Autor:Liñares, G.E.G.; Rodriguez, J.B.
Filiación:Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, C1428EHA Buenos Aires, Argentina
Palabras clave:Chloroquine; Cysteine proteases; Farnesyltransferase inhibitors; Piperazine derivatives; Plasmodium falciparum; 4 aminoquinoline derivative; aminobenzenesulfonamide derivative; aminophenol derivative; amodiaquine; antimalarial agent; artemisinin; artemisinin derivative; artemisone; chloroquine; cysteine proteinase; dihydroartemisinin; dihydrofolate reductase; falcipain inhibitor; fatty acid; fatty acid synthase inhibitor; heme; hemoglobin; mefloquine; mepacrine; methylpiperazine derivative; polyamine; protein farnesyltransferase; proteinase; pyrimethamine; pyronaridine; quinine; quinoline derivative; sulfonamide; thioacridone derivative; unclassified drug; unindexed drug; antimalarial agent; artemisinin; artemisinin derivative; cysteine proteinase; cysteine proteinase inhibitor; falcipain; fatty acid; glutathione; glutathione transferase; hemoprotein; hemozoin; p21(ras) farnesyl protein transferase; p21(ras) farnesyl-protein transferase; polyamine; sesquiterpene; thioredoxin; transferase; antimalarial activity; biochemistry; chemotherapy; drug bioavailability; drug design; drug half life; drug potency; drug potentiation; drug structure; human; IC 50; in vitro study; in vivo study; malaria control; malaria falciparum; neurotoxicity; nonhuman; parasite survival; parasitosis; Plasmodium falciparum; review; structure activity relation; animal; biosynthesis; drug antagonism; drug effect; drug resistance; malaria; metabolism; physiology; Alkyl and Aryl Transferases; Animals; Antimalarials; Artemisinins; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Drug Resistance; Fatty Acids; Glutathione; Glutathione Transferase; Hemeproteins; Humans; Malaria; Plasmodium falciparum; Polyamines; Sesquiterpenes; Structure-Activity Relationship; Thioredoxin
Año:2007
Volumen:14
Número:3
Página de inicio:289
Página de fin:314
DOI: http://dx.doi.org/10.2174/092986707779941096
Título revista:Current Medicinal Chemistry
Título revista abreviado:Curr. Med. Chem.
ISSN:09298673
CODEN:CMCHE
CAS:amodiaquine, 69-44-3, 86-42-0; artemisinin, 63968-64-9; chloroquine, 132-73-0, 3545-67-3, 50-63-5, 54-05-7; cysteine proteinase, 37353-41-6; dihydroartemisinin, 71939-50-9, 81496-81-3; dihydrofolate reductase, 9002-03-3; heme, 14875-96-8; hemoglobin, 9008-02-0; mefloquine, 51773-92-3, 53230-10-7; mepacrine, 69-05-6, 83-89-6; proteinase, 9001-92-7; pyrimethamine, 53640-38-3, 58-14-0; pyronaridine, 74847-35-1; quinine, 130-89-2, 130-95-0, 14358-44-2, 549-48-4, 549-49-5, 60-93-5, 7549-43-1; glutathione, 70-18-8; glutathione transferase, 50812-37-8; hemozoin, 39404-00-7; thioredoxin, 52500-60-4; transferase, 9047-61-4; Alkyl and Aryl Transferases, 2.5.-; Antimalarials; Artemisinins; Cysteine Endopeptidases, 3.4.22.-; Cysteine Proteinase Inhibitors; Fatty Acids; Glutathione, 70-18-8; Glutathione Transferase, 2.5.1.18; Hemeproteins; Polyamines; Sesquiterpenes; Thioredoxin, 52500-60-4; artemisinine, 63968-64-9; falcipain, 3.4.22.-; hemozoin, 39404-00-7; p21(ras) farnesyl-protein transferase, 2.5.1.-
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09298673_v14_n3_p289_Linares

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Citas:

---------- APA ----------
Liñares, G.E.G. & Rodriguez, J.B. (2007) . Current status and progress made in malaria chemotherapy. Current Medicinal Chemistry, 14(3), 289-314.
http://dx.doi.org/10.2174/092986707779941096
---------- CHICAGO ----------
Liñares, G.E.G., Rodriguez, J.B. "Current status and progress made in malaria chemotherapy" . Current Medicinal Chemistry 14, no. 3 (2007) : 289-314.
http://dx.doi.org/10.2174/092986707779941096
---------- MLA ----------
Liñares, G.E.G., Rodriguez, J.B. "Current status and progress made in malaria chemotherapy" . Current Medicinal Chemistry, vol. 14, no. 3, 2007, pp. 289-314.
http://dx.doi.org/10.2174/092986707779941096
---------- VANCOUVER ----------
Liñares, G.E.G., Rodriguez, J.B. Current status and progress made in malaria chemotherapy. Curr. Med. Chem. 2007;14(3):289-314.
http://dx.doi.org/10.2174/092986707779941096