Combination Therapy for Malaria: Mission Accomplished?

Clinical Infectious Diseases (Impact Factor: 8.89). 05/2007; 44(8):1075-7. DOI: 10.1086/512743
Source: PubMed

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    ABSTRACT: Malaria is a significant cause of morbidity and mortality in the developing world. Until recently malaria was winning but with increase in funding particularly from philanthropic groups the ability to control malaria is again possible. There are still many challenges to developing the next generations of anti-malarials. This article will briefly discuss the challenges and the advance that are being made.
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    ABSTRACT: Nine dihydroartemisinin acetal dimers (6-14) with diversely functionalized linker units were synthesized and tested for in vitro antiprotozoal, anticancer and antimicrobial activity. Compounds 6, 7 and 11 [IC(50): 3.0-6.7 nM (D6) and 4.2-5.9 nM (W2)] were appreciably more active than artemisinin (1) [IC(50): 32.9 nM (D6) and 42.5 nM (W2)] against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of the malaria parasite, Plasmodium falciparum. Compounds 10, 13 and 14 displayed enhanced anticancer activity in a number of cell lines compared to the control drug, doxorubicin. The antifungal activity of 7 and 12 against Cryptococcus neoformans (IC(50): 0.16 and 0.55 microM, respectively) was also higher compared to the control drug, amphotericin B. The antileishmanial and antibacterial activities were marginal. A number of dihydroartemisinin acetal monomers (15-17) and a trimer (18) were isolated as byproducts from the dimer synthesis and were also tested for biological activity.
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    ABSTRACT: Antimalarial drugs are medicines that prevent or treat malaria, a disease which takes a great toll on human health and well-being, particularly in tropical regions including Africa south of the Sahara, South and Southeast Asia, Oceania, and parts of the Americas. In recent years, strains of Plasmodium have become increasingly resistant to more antimalarial drugs and researchers have stepped up efforts to revise antimalarial drug policies and develop new antimalarial strategies. Resistance has arisen to all classes of antimalarials (chloroquine, amodiaquine, mefloquine and sulfadoxine-pyrimethamine) except, as yet, definitively to the artemisinin derivatives. In order to prevent widespread resistance, the concept of antimalarial combination therapy (CT) has been employed and a global resistance surveillance system (World Antimalarial Resistance Networks) has been established. This book explores the use of these drugs in current health care.
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