Malaria Chemotherapy: Recent Advances in Drug Development

Sandra      Gemma; Valter      Travagli; Luisa      Savini; Ettore      Novellino; Giuseppe      Campiani; Stefania      Butini

Abstract

Malaria is a disease caused by parasitic protozoa of the genus Plasmodium. Despite significant advances in understanding the disease and the parasite biology, malaria still remains one of the leading causes of morbidity and mortality, particularly in malaria-endemic regions of the world. The main factor hampering malaria control is the high degree of resistance developed by Plasmodium species against several classes of drugs. Artemisinin-based Combination Therapy (ACT) is the most rapidly acting antimalarial treatment effective against multi-drug resistant strains, and is, at present, the only group of antimalarial drugs to which resistance by Plasmodium falciparum has not developed yet in the field, even though the isolation of artemisinin-resistant strains is raising concern. As a result, discovering and developing novel antimalarial agents is one of the greatest challenges facing malaria control today. This review covers patent literature from 2007 to date regarding small molecules or natural compounds targeting the asexual forms of the parasite. Recent patents filed and issued for ameliorating conventional antimalarial treatment methods by non-conventional dosage forms are also reviewed.

Keywords: Drug resistant malaria, heme detoxification, protease inhibitors, drug delivery, Chemotherapy, Plasmodium, Artemisinin-based Combination Therapy, Plasmodium falciparum, MMV, DNDi, IMN, quinolines, chloroquine, antifolates, peroxides, hydroxynaphthoquinone atovaquone, Mefloquine, Amodiaquine, Pyrimethamine, Sulfadoxine, Artemisinin, Atovaquone, monotherapy, parasitophorous vacuole, trophozoite, schizont, egress, antimalarial drugs, Heme/Haemoglobin, plasmepsins, falcipains, falcilysin, oxyferro-protoporphyrin, hydroxyferri-protoporphyrin, detoxification, Hematin, Hemozoin, Sigma-Tau, P. berghei, antiplasmodial, clotrimazole, imidazole, pharmacophore, SARs, P. chabaudi, Plasmodia, Febrifugine, Baylis Hillman adducts, 4-quinolinomethanols, Doxovir, histidines, chlorpheniramine, orphenadrine, voacamine, Artemisia annua, Eurartesim, ASAQ, Coartemamodiaquine, Coarsucam, SERCA, parasitaemia, Dihydroartemisinin (DHA), Artemether, Arteether, Artesunate, Artemisone, Synthetic Peroxides, P. yoelii, Tetraoxaspiro[7.11]nonadecane, Adenosine deaminase, dihydrofolate reductase, Purine Salvage Pathway, dihydroorotate dehydrogenase, P. vivax, P. c. adami, Isoprenoid, Histone Deacetylase, Protein Kinase, glutathione reductases, pantetheinase, Heat shock protein, geldanamycin, ansamycins, Glycosylphosphatidylinositol, Azithromycin, Aigialomycin, Gomphostenin, Gomphostema niveum, Aculeatines, laurocapram, Chromobacterium violaceum, arteannuin, naphthoquine, CN101474152