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Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an\n                    <jats:italic>in vivo<\/jats:italic>\n                    model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na\n                    <jats:sup>+<\/jats:sup>\n                    regulation in blood-stage\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    parasites. Similar effect on Na\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes.\n                  <\/jats:p>","DOI":"10.1038\/ncomms6521","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T10:57:28Z","timestamp":1416913048000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum"],"prefix":"10.1038","volume":"5","author":[{"given":"Akhil B.","family":"Vaidya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne 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