{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:14:31Z","timestamp":1790172871793,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Artemisinin (ART) resistance has spread through Southeast Asia, posing a serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            kelch-13 (\n            <jats:italic>Pfk13<\/jats:italic>\n            ) propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence. These quiescent rings are referred to as dormant rings or DHA-pretreated rings (here called dormant rings). The imidazolopiperazines (IPZ) are a novel class of antimalarial drugs that have demonstrated efficacy in early clinical trials. Here, we characterized the stage of action of the IPZ GNF179 and evaluated its activity against rings and dormant rings in wild-type and ART-resistant parasites. Unlike DHA, GNF179 does not induce dormancy. We show that GNF179 is more rapidly cidal against schizonts than against ring and trophozoite stages. However, with 12 h of exposure, the compound effectively kills rings and dormant rings of both susceptible and ART-resistant parasites within 72 h. We further demonstrate that in combination with ART, GNF179 effectively prevents recrudescence of dormant rings, including those bearing\n            <jats:italic>pfk13<\/jats:italic>\n            propeller mutations.\n          <\/jats:p>","DOI":"10.1128\/aac.02235-17","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T15:51:57Z","timestamp":1520524317000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Imidazolopiperazines Kill both Rings and Dormant Rings in Wild-Type and K13 Artemisinin-Resistant Plasmodium falciparum In Vitro"],"prefix":"10.1128","volume":"62","author":[{"given":"Laurent","family":"Dembele","sequence":"first","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"},{"name":"Universit\u00e9 des Sciences, des Techniques et des Technologies de Bamako (USTTB), MRTC\u2013DEAP\u2013Faculty of Pharmacy, Bamako, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devendra Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Yi-Xiu","family":"Lim","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Ang","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy J.","family":"Selva","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesinee","family":"Chotivanich","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"},{"name":"Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chea","family":"Nguon","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen M.","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Mahidol-Oxford Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"},{"name":"Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislain M. C.","family":"Bonamy","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry T.","family":"Diagana","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Bifani","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore"},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Singapore Immunology Network (SIgN), A*STAR, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World malaria report","author":"WHO","year":"2015","unstructured":"WHO. 2015. 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