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We identified a novel class of compounds in the antimalarial armory. Compound\n                    <jats:bold>31<\/jats:bold>\n                    , characterized by a 2\u2010hydroxyphenyl benzamide scaffold, displays potent activity against blood\u2010stage and mature sexual stages of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and no toxicity in human cells. Resistance selection studies with\n                    <jats:bold>31<\/jats:bold>\n                    identified a previously unknown point mutation in the\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    multidrug\u2010resistance protein 1 (\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    ) gene, for which we confirmed causality by CRISPR\/Cas9\u2010based gene editing as the primary mediator of resistance. No cross\u2010resistance toward first\u2010line antimalarials was identified in compound\n                    <jats:bold>31<\/jats:bold>\n                    \u2010resistant parasites. Proteomics studies indicated that the primary mode of action of\n                    <jats:bold>31<\/jats:bold>\n                    is through direct binding to cytosolic ribosomal subunits, thereby inhibiting protein synthesis in the parasite. Taken together, compound\n                    <jats:bold>31<\/jats:bold>\n                    is a promising starting point for the development of a next\u2010generation antimalarial.\n                  <\/jats:p>","DOI":"10.1002\/anie.202514085","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:13:08Z","timestamp":1761019988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Antimalarial Agent that Inhibits Protein Synthesis in\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1002","volume":"64","author":[{"given":"Patricia","family":"Bravo","sequence":"first","affiliation":[{"name":"Medical Parasitology and Infection Biology Swiss Tropical and Public Health Institute  Kreuzstrasse 2 Allschwil 4123 Switzerland"},{"name":"Universit\u00e4t Basel  Petersplatz 1 Basel 4003 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8392-5575","authenticated-orcid":false,"given":"Eleonora","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)\u2500Helmholtz Centre for Infection Research (HZI) PharmaScienceHub  Campus Building E8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa M.","family":"Hamed","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)\u2500Helmholtz Centre for Infection Research (HZI) PharmaScienceHub  Campus Building E8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Bizzarri","sequence":"additional","affiliation":[{"name":"OmicScouts GmbH  Lise\u2010Meitner\u2010Stra\u00dfe 30 D\u201085354 Freising Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Wiedemar","sequence":"additional","affiliation":[{"name":"Medical Parasitology and Infection Biology Swiss Tropical and Public Health Institute  Kreuzstrasse 2 Allschwil 4123 Switzerland"},{"name":"Universit\u00e4t Basel  Petersplatz 1 Basel 4003 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Passecker","sequence":"additional","affiliation":[{"name":"Medical Parasitology and Infection Biology Swiss Tropical and Public Health Institute  Kreuzstrasse 2 Allschwil 4123 Switzerland"},{"name":"Universit\u00e4t Basel  Petersplatz 1 Basel 4003 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas M. 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