Matthias RottmannCase McNamaraBryan K.S. YeungMarcus C.S. LeeBin ZouBruce RussellPatrick SeitzDavid M. PlouffeNeekesh V. DhariaJocelyn TanSteven B. CohenKathryn R. SpencerGonzalo E. González-PáezSuresh B. LakshminarayanaAnne GohRossarin SuwanaruskTimothy JeglaEsther K. SchmittHans Peter BeckReto BrunFrancois NostenLaurent ReniaVeronique DartoisThomas H. KellerDavid A. FidockElizabeth A. WinzelerThierry T. DiaganaSwiss Tropical and Public Health Institute (Swiss TPH)Universitat BaselThe Genomics Institute of the Novartis Research FoundationNovartis Institute for Tropical Diseases Pte. Ltd.Columbia University Medical CenterAgency for Science, Technology and Research, SingaporeNational University of SingaporeScripps Research InstitutePennsylvania State UniversityNovartis International AGShoklo Malaria Research UnitMahidol UniversityNuffield Department of Clinical Medicine2018-09-242018-09-242010-09-03Science. Vol.329, No.5996 (2010), 1175-118010959203003680752-s2.0-77956280420https://repository.li.mahidol.ac.th/handle/123456789/29981Recent reports of increased tolerance to artemisinin derivatives - the most recently adopted class of antimalarials - have prompted a need for new treatments. The spirotetrahydro-β-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.1126/science.1193225