{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:54:16Z","timestamp":1787320456971,"version":"build-2736575974"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"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":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Novel synthetic endoperoxides are being evaluated as new components of artemisinin combination therapies (ACTs) to treat artemisinin-resistant\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                    malaria. We conducted blinded\n                    <jats:italic>ex vivo<\/jats:italic>\n                    activity testing of fully synthetic (OZ78 and OZ277) and semisynthetic (artemisone, artemiside, artesunate, and dihydroartemisinin) endoperoxides in the histidine-rich protein 2 enzyme-linked immunosorbent assay against 200\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    isolates from areas of artemisinin-resistant malaria in western and northern Cambodia in 2009 and 2010. The order of potency and geometric mean (GM) 50% inhibitory concentrations (IC\n                    <jats:sub>50<\/jats:sub>\n                    s) were as follows: artemisone (2.40 nM) &gt; artesunate (8.49 nM) &gt; dihydroartemisinin (11.26 nM) &gt; artemiside (15.28 nM) &gt; OZ277 (31.25 nM) &gt; OZ78 (755.27 nM).\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    activities of test endoperoxides positively correlated with dihydroartemisinin and artesunate. The isolates were over 2-fold less susceptible to dihydroartemisinin than the artemisinin-sensitive\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    W2 clone and showed sensitivity comparable to those with test endoperoxides and artesunate, with isolate\/W2 IC\n                    <jats:sub>50<\/jats:sub>\n                    susceptibility ratios of &lt;2.0. All isolates had\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    chloroquine resistance transporter mutations, with negative correlations in sensitivity to endoperoxides and chloroquine. The activities of endoperoxides (artesunate, dihydroartemisinin, OZ277, and artemisone) significantly correlated with that of the ACT partner drug, mefloquine. Isolates had mutations associated with clinical resistance to mefloquine, with 35% prevalence of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    multidrug resistance gene 1 (\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    ) amplification and 84.5% occurrence of the\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    Y184F mutation. GM IC\n                    <jats:sub>50<\/jats:sub>\n                    s for mefloquine, lumefantrine, and endoperoxides (artesunate, dihydroartemisinin, OZ277, OZ78, and artemisone) correlated with\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    copy number. Given that current ACTs are failing potentially from reduced sensitivity to artemisinins and partner drugs, newly identified mutations associated with artemisinin resistance reported in the literature and\n                    <jats:italic>pfmdr1<\/jats:italic>\n                    mutations should be examined for their combined contributions to emerging ACT resistance.\n                  <\/jats:p>","DOI":"10.1128\/aac.02462-14","type":"journal-article","created":{"date-parts":[[2014,7,21]],"date-time":"2014-07-21T23:15:21Z","timestamp":1405984521000},"page":"5831-5840","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["<i>Ex Vivo<\/i>\n                    Activity of Endoperoxide Antimalarials, Including Artemisone and Arterolane, against Multidrug-Resistant Plasmodium falciparum Isolates from Cambodia"],"prefix":"10.1128","volume":"58","author":[{"given":"Charlotte A.","family":"Lanteri","sequence":"first","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suwanna","family":"Chaorattanakawee","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanthap","family":"Lon","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiriya","family":"Rutvisuttinunt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kritsanai","family":"Yingyuen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Bathurst","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier C.","family":"Ding","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart 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