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Despite the current need, there is no effective vaccine and parasites are becoming resistant to most of the antimalarials available. Therefore, there is an urgent need to discover new drugs from targets that have not yet suffered from drug pressure with the aim of overcoming the problem of new emerging resistance. Membrane transporters, such as P<\/jats:styled-content>.\u00a0falciparum <\/jats:italic>C<\/jats:styled-content>a2+<\/jats:sup>\u2010ATP<\/jats:styled-content>ase 6 (P<\/jats:styled-content>fATP<\/jats:styled-content>6), the P<\/jats:styled-content>.\u00a0falciparum<\/jats:italic> sarcoplasmic\/endoplasmic reticulum C<\/jats:styled-content>a2+<\/jats:sup>\u2010ATP<\/jats:styled-content>ase (SERCA<\/jats:styled-content>), have been proposed as potentially good antimalarial targets. The present investigation focuses on: (a) the large\u2010scale purification of P<\/jats:styled-content>fATP<\/jats:styled-content>6 for maintenance of its enzymatic activity; (b) screening for P<\/jats:styled-content>fATP<\/jats:styled-content>6 inhibitors from a compound library; and (c) the selection of the best inhibitors for further tests on P<\/jats:styled-content>.\u00a0falciparum<\/jats:italic> growth in\u00a0vitro<\/jats:italic>. We managed to heterologously express in yeast and purify an active form of P<\/jats:styled-content>fATP<\/jats:styled-content>6 as previously described, although in larger amounts. In addition to some classical SERCA<\/jats:styled-content> inhibitors, a chemical library of 1680 molecules was screened. From these, we selected a pool of the 20 most potent inhibitors of P<\/jats:styled-content>fATP<\/jats:styled-content>6, presenting half maximal inhibitory concentration values in the range 1\u20139\u00a0\u03bcm<\/jats:sc>. From these, eight were chosen for evaluation of their effect on P<\/jats:styled-content>.\u00a0falciparum<\/jats:italic> growth in\u00a0vitro<\/jats:italic>, and the best compound presented a half maximal inhibitory concentration of ~\u00a02\u00a0\u03bcm<\/jats:sc>. We verified the absence of an inhibitory effect of most of the compounds on mammalian SERCA<\/jats:styled-content>1a, representing a potential advantage in terms of human toxicity. The present study describes a multidisciplinary approach allowing the selection of promising P<\/jats:styled-content>fATP<\/jats:styled-content>6\u2010specific inhibitors with good antimalarial activity.<\/jats:p>","DOI":"10.1111\/febs.12244","type":"journal-article","created":{"date-parts":[[2013,3,17]],"date-time":"2013-03-17T02:16:30Z","timestamp":1363486590000},"page":"5419-5429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antimalarial screening via large\u2010scale purification of P<\/scp>lasmodium falciparum <\/i>C<\/scp>a2+<\/sup>\u2010ATP<\/scp>ase 6 and in\u00a0vitro<\/i> studies"],"prefix":"10.1111","volume":"280","author":[{"given":"St\u00e9phanie","family":"David\u2010Bosne","sequence":"first","affiliation":[{"name":"UMR 8221 CNRS Universit\u00e9 Paris\u2010Sud and CEA Gif\u2010sur\u2010Yvette 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