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Carbonic anhydrase inhibitors: Inhibition of Plasmodium falciparum carbonic anhydrase with aromatic/heterocyclic sulfonamides—in vitro and in vivo studies

Malaria, a major parasitic disease of humans, is caused by protozoa of the genus Plasmodium , classified in the phylum Apicomplexa. 1 The disease afflicts 515 million and kills 1.5–2.7 million people each year, most of whom children in sub-Saharan Africa. 2–6 P. falciparum is responsible for most of these deaths. 2,6 In addition to the lack of effective vector control and vaccines, the limitations and toxicity of antimalarial drugs in current use, and the spread of drug-resistant malaria accompanied by a worldwide resurgence of the disease, highlights the need to develop quickly more effective and less toxic novel antimalarial drugs, possessing a different mechanism of action. 5,7–10 Drug screening procedures have rarely been applied to identify lead molecules for this disease, and there is a paucity of information on a number of metabolic pathways that can be exploited for malaria chemotherapy. 7–9 A better understanding of biochemical differences between the parasite and human metabolic processes may provide new targets for intervention in the fight against this disease. 10 In 1998, Sein and Aikawa 11 proved the in situ carbonic anhydrase (CA, EC activity in P. falciparum -infected red blood cells by using electron microscopy and CA-specific http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Bioorganic & Medicinal Chemistry Letters Elsevier
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