{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:22:09Z","timestamp":1790670129531,"version":"4.1.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Despite declining numbers of cases and deaths, malaria remains a major public health problem in many parts of the world. Today, case management relies heavily on a single class of antimalarial compounds: artemisinins. Hence, development of resistance against artemisinins may destroy current malaria control strategies. Beyond malaria control are elimination and eradication programs that will require drugs with good activity against acute infection but also with preventive and transmission-blocking properties. Consequently, new antimalarials are needed not only to ensure malaria control but also for elimination and eradication efforts. In this study, we introduce peptido sulfonyl fluorides (PSF) as a new class of compounds with antiplasmodial activity. We show that PSF target the plasmodial proteasome and act on all asexual stages of the intraerythrocytic cycle and on gametocytes. PSF showed activities at concentrations as low as 20 nM against multidrug-resistant and chloroquine-sensitive\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            laboratory strains and clinical isolates from Gabon. Structural requirements for activity were identified, and cytotoxicity in human HeLa or HEK 293 cells was low. The lead PSF PW28 suppressed growth of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium berghei<\/jats:named-content>\n            <jats:italic>in vivo<\/jats:italic>\n            but showed signs of toxicity in mice. Considering their modular structure and broad spectrum of activity against different stages of the plasmodial life cycle, proteasome inhibitors based on PSF have a great potential for further development as preclinical candidate compounds with improved species-specific activity and less toxicity.\n          <\/jats:p>","DOI":"10.1128\/aac.00742-12","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T05:04:18Z","timestamp":1369112658000},"page":"3576-3584","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Broad-Spectrum Antimalarial Activity of Peptido Sulfonyl Fluorides, a New Class of Proteasome Inhibitors"],"prefix":"10.1128","volume":"57","author":[{"given":"Serena","family":"Tschan","sequence":"first","affiliation":[{"name":"University of T\u00fcbingen, Institute of Tropical Medicine, and German Centre for Infection Research, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwin J.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Utrecht University, Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Werkhoven","sequence":"additional","affiliation":[{"name":"Utrecht University, Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika M.","family":"Jonker","sequence":"additional","affiliation":[{"name":"Utrecht University, Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Wagner","sequence":"additional","affiliation":[{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Knittel","sequence":"additional","affiliation":[{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoah Nigel","family":"Aminake","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg, Research Center for Infectious Diseases, W\u00fcrzburg, Germany"},{"name":"RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Pradel","sequence":"additional","affiliation":[{"name":"University of W\u00fcrzburg, Research Center for Infectious Diseases, W\u00fcrzburg, Germany"},{"name":"RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Joanny","sequence":"additional","affiliation":[{"name":"University of T\u00fcbingen, Institute of Tropical Medicine, and German Centre for Infection Research, T\u00fcbingen, Germany"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob M. J.","family":"Liskamp","sequence":"additional","affiliation":[{"name":"Utrecht University, Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands"},{"name":"School of Chemistry, Chemical Biology and Medicinal Chemistry, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mordm\u00fcller","sequence":"additional","affiliation":[{"name":"University of T\u00fcbingen, Institute of Tropical Medicine, and German Centre for Infection Research, T\u00fcbingen, Germany"},{"name":"Centre de Recherches M\u00e9dicales de Lambar\u00e9n\u00e9, Lambar\u00e9n\u00e9, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44423"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/156652406776055122"},{"key":"e_1_3_3_4_2","volume-title":"World malaria report 2011","author":"Aregawi M","year":"2011","unstructured":"AregawiM CibulskisRE LynchM WilliamsR, World Health Organization Global Malaria Programme. 2011. 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