{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:53:39Z","timestamp":1761929619414},"reference-count":46,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n The declining efficacy of artemisinin derivatives against\n Plasmodium falciparum<\/jats:named-content>\n highlights the urgent need to identify alternative highly potent compounds for the treatment of malaria. In Papua Indonesia, where multidrug resistance has been documented against both\n P. falciparum<\/jats:named-content>\n and\n P. vivax<\/jats:named-content>\n malaria, comparative\n ex vivo<\/jats:italic>\n antimalarial activity against\n Plasmodium<\/jats:named-content>\n isolates was assessed for the artemisinin derivatives artesunate (AS) and dihydroartemisinin (DHA), the synthetic peroxides OZ277 and OZ439, the semisynthetic 10-alkylaminoartemisinin derivatives artemisone and artemiside, and the conventional antimalarial drugs chloroquine (CQ), amodiaquine (AQ), and piperaquine (PIP).\n Ex vivo<\/jats:italic>\n drug susceptibility was assessed in 46 field isolates (25\n P. falciparum<\/jats:named-content>\n and 21\n P. vivax<\/jats:named-content>\n ). The novel endoperoxide compounds exhibited potent\n ex vivo<\/jats:italic>\n activity against both species, but significant differences in intrinsic activity were observed. Compared to AS and its active metabolite DHA, all the novel compounds showed lower or equal 50% inhibitory concentrations (IC\n 50<\/jats:sub>\n s) in both species (median IC\n 50<\/jats:sub>\n s between 1.9 and 3.6 nM in\n P. falciparum<\/jats:named-content>\n and 0.7 and 4.6 nM in\n P. vivax<\/jats:named-content>\n ). The antiplasmodial activity of novel endoperoxides showed different cross-susceptibility patterns in the two\n Plasmodium<\/jats:named-content>\n species: whereas their\n ex vivo<\/jats:italic>\n activity correlated positively with CQ, PIP, AS, and DHA in\n P. falciparum<\/jats:named-content>\n , the same was not apparent in\n P. vivax<\/jats:named-content>\n . The current study demonstrates for the first time potent activity of novel endoperoxides against drug-resistant\n P. vivax<\/jats:named-content>\n . The high activity against drug-resistant strains of both\n Plasmodium<\/jats:named-content>\n species confirms these compounds to be promising candidates for future artemisinin-based combination therapy (ACT) regimens in regions of coendemicity.\n <\/jats:p>","DOI":"10.1128\/aac.00283-12","type":"journal-article","created":{"date-parts":[[2012,7,31]],"date-time":"2012-07-31T07:47:26Z","timestamp":1343720846000},"page":"5258-5263","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Comparative\n Ex Vivo<\/i>\n Activity of Novel Endoperoxides in Multidrug-Resistant Plasmodium falciparum and P. vivax"],"prefix":"10.1128","volume":"56","author":[{"given":"Jutta","family":"Marfurt","sequence":"first","affiliation":[{"name":"Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferryanto","family":"Chalfein","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pak","family":"Prayoga","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans","family":"Wabiser","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grennady","family":"Wirjanata","sequence":"additional","affiliation":[{"name":"Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boni","family":"Sebayang","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology, Jakarta, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim A.","family":"Piera","sequence":"additional","affiliation":[{"name":"Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Wittlin","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard K.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg J.","family":"M\u00f6hrle","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture (MMV), Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Anstey","sequence":"additional","affiliation":[{"name":"Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enny","family":"Kenangalem","sequence":"additional","affiliation":[{"name":"Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia"},{"name":"District Ministry of Health, Timika, Papua, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ric N.","family":"Price","sequence":"additional","affiliation":[{"name":"Global Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia"},{"name":"Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.4269\/ajtmh.1995.53.639","article-title":"Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine","volume":"53","author":"Alin MH","year":"1995","unstructured":"AlinMH. 1995. Efficacy of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine, and mefloquine. Am. J. Trop. Med. Hyg. 53:639\u2013645.","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-6-120"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.2174\/138920111798376923","article-title":"Searching for artemisinin production improvement in plants and microorganisms","volume":"12","author":"Barbacka K","year":"2011","unstructured":"BarbackaK Baer-DubowskaW. 2011. Searching for artemisinin production improvement in plants and microorganisms. Curr. Pharm. Biotechnol. 12:1743\u20131751.","journal-title":"Curr. Pharm. Biotechnol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(00)90080-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.1073\/pnas.1015762108","article-title":"Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria","volume":"108","author":"Charman SA","year":"2011","unstructured":"CharmanSA. 2011. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc. Natl. Acad. Sci. U. S. A. 108:4400\u20134405.","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70079-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61270-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)01043-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1002\/anie.200503071","article-title":"Artemisone\u2014a highly active antimalarial drug of the artemisinin class","volume":"45","author":"Haynes RK","year":"2006","unstructured":"HaynesRK. 2006. Artemisone\u2014a highly active antimalarial drug of the artemisinin class. Angew. Chem. Int. ed Engl. 45:2082\u20132088.","journal-title":"Angew. Chem. Int. ed Engl."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1093\/jac\/dkn315","article-title":"In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum","volume":"62","author":"Hofer S","year":"2008","unstructured":"HoferS. 2008. In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum. J. Antimicrob. Chemother. 62:1061\u20131064.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-148"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/1475-2875-6-125","article-title":"Ensuring sustained ACT production and reliable artemisinin supply","volume":"6","author":"Kindermans JM","year":"2007","unstructured":"KindermansJM PilloyJ OlliaroP GomesM. 2007. Ensuring sustained ACT production and reliable artemisinin supply. Malar. J. 6:125.","journal-title":"Malar. J."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2005.12.016"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2006.02.006"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.75.1178"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1535-1537.2006"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-8-11"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl209"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01220-10"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.64.97"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01585-07"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.pt.2005.06.012","article-title":"Artemisinin resistance: how can we find it?","volume":"21","author":"Noedl H","year":"2005","unstructured":"NoedlH. 2005. Artemisinin resistance: how can we find it? Trends Parasitol. 21:404\u2013405.","journal-title":"Trends Parasitol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0805011"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0900231"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.65.696"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00471-09"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.51"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2007.76.1024"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1086\/586743"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/1475-2875-10-268","article-title":"Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia","volume":"10","author":"Pradines B","year":"2011","unstructured":"PradinesB BertauxL PomaresC DelaunayP MartyP. 2011. Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia. Malar. J. 10:268.","journal-title":"Malar. J."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32832f14c1"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2006.06.008"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01334-07"},{"key":"e_1_3_2_36_2","unstructured":"Reference deleted."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-94"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1086\/596738"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1046\/j.1365-2125.2000.00176.x","article-title":"In vitro sensitivity of Plasmodium falciparum and clinical response to lumefantrine (benflumetol) and artemether","volume":"49","author":"Tanariya P","year":"2000","unstructured":"TanariyaP TippawangkosoP KarbwangJ Na-BangchangK WernsdorferWH. 2000. In vitro sensitivity of Plasmodium falciparum and clinical response to lumefantrine (benflumetol) and artemether. Br. J. Clin. Pharmacol. 49:437\u2013444.","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/1475-2875-9-181","article-title":"Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009","volume":"9","author":"Thanh NV","year":"2010","unstructured":"ThanhNV. 2010. Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009. Malar. J. 9:181.","journal-title":"Malar. J."},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.1.105-109.2002"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-227"},{"key":"e_1_3_2_43_2","volume-title":"Malaria: principles and practice of malariology.","author":"Wernsdorfer WH","year":"1989","unstructured":"WernsdorferWH McGregorI. 1989. Malaria: principles and practice of malariology. Churchill Livingstone, Edinburgh, Scotland."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01636-09"},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.4269\/ajtmh.2001.65.450","article-title":"In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs","volume":"65","author":"Wongsrichanalai C","year":"2001","unstructured":"WongsrichanalaiC. 2001. In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs. Am. J. Trop. Med. Hyg. 65:450\u2013455.","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"e_1_3_2_46_2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. Guidelines for the treatment of malaria, 2nd ed. World Health Organization, Geneva, Switzerland.","edition":"2"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.30875\/b51b2f2c-en"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00283-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00283-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:00:06Z","timestamp":1645480806000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00283-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1128\/AAC.00283-12"],"URL":"https:\/\/doi.org\/10.1128\/aac.00283-12","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10]]},"assertion":[{"value":"2012-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}