{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:34:49Z","timestamp":1783658089632,"version":"3.55.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Medicine for Malaria Venture"},{"name":"Pasteur Institute International Network"},{"name":"Initiative 5% Grant (MIVS-ACT","award":["15SANIN211"],"award-info":[{"award-number":["15SANIN211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Expanding resistance to multiple antimalarials, including chloroquine, in South-East Asia (SEA) urges the development of new therapies. AQ-13, a chloroquine derivative, is a new drug candidate for treating malaria caused by Plasmodium falciparum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Possible cross-resistance between the 4-aminoquinolines amodiaquine, piperaquine and AQ-13 has not been assessed. In vitro parasite growth assays were used to characterize the susceptibility of multidrug-resistant and susceptible P. falciparum patient isolates to AQ-13.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A [3H]hypoxanthine uptake assay and a 384-well high content imaging assay were used to assess efficacy of AQ-13 and desethyl-amodiaquine against 38 P. falciparum isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed a strong cross-resistance between the chloroquine derivative amodiaquine and AQ-13 in Cambodian P. falciparum isolates (Pearson correlation coefficient of 0.8621, P\u200a&amp;lt;\u200a0.0001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In light of the poor efficacy of amodiaquine that we described recently in Cambodia, and its cross resistance with AQ-13, there is a significant risk that similar clinical efficacy of AQ-13-based combinations should be anticipated in areas of amodiaquine resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab219","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:09:49Z","timestamp":1624532989000},"page":"2565-2568","source":"Crossref","is-referenced-by-count":9,"title":["Cross-resistance of the chloroquine-derivative AQ-13 with amodiaquine in Cambodian <i>Plasmodium falciparum<\/i> isolates"],"prefix":"10.1093","volume":"76","author":[{"given":"Flore","family":"Nardella","sequence":"first","affiliation":[{"name":"Unit\u00e9 Biologie des Interactions H\u00f4te-Parasite, D\u00e9partement de Parasites et Insectes Vecteurs, Institut Pasteur, CNRS ERL9195, INSERM Unit U1201, 25\u201328 Rue du Dr Roux, Paris, 75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lissa","family":"Mairet-Khedim","sequence":"additional","affiliation":[{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Roesch","sequence":"additional","affiliation":[{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P","family":"Maher","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D.W. Brooks Dr., Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sopheakvatey","family":"Ke","sequence":"additional","affiliation":[{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rithea","family":"Leang","sequence":"additional","affiliation":[{"name":"National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Leroy","sequence":"additional","affiliation":[{"name":"Medicine for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Malaria Molecular Epidemiology Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,10]]},"reference":[{"key":"2021091709024898400_dkab219-B1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0169-4758(87)90147-5","article-title":"Spread of chloroquine resistance in Plasmodium falciparum","volume":"3","author":"Payne","year":"1987","journal-title":"Parasitol Today"},{"key":"2021091709024898400_dkab219-B2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.4269\/ajtmh.12-0671","article-title":"Efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum Malaria in Honduras","volume":"88","author":"Torres","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"2021091709024898400_dkab219-B3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/s41586-019-1795-x","article-title":"Structure and drug resistance of the Plasmodium falciparum transporter PfCRT","volume":"576","author":"Kim","year":"2019","journal-title":"Nature"},{"key":"2021091709024898400_dkab219-B4","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1038\/s41467-018-05652-0","article-title":"Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine","volume":"9","author":"Ross","year":"2018","journal-title":"Nat Commun"},{"key":"2021091709024898400_dkab219-B5","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/S1473-3099(19)30543-2","article-title":"Plasmodium falciparum resistance to piperaquine driven by PfCRT","volume":"19","author":"Dhingra","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2021091709024898400_dkab219-B6","article-title":"Clinical and in vitro resistance of Plasmodium falciparum to artesunate-amodiaquine in Cambodia","author":"Mairet-Khedim","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021091709024898400_dkab219-B7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/13543784.2019.1560419","article-title":"AQ-13 - an investigational antimalarial drug","volume":"28","author":"Mengue","year":"2019","journal-title":"Expert Opin Investig Drugs"},{"key":"2021091709024898400_dkab219-B8","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/S1473-3099(17)30365-1","article-title":"AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial","volume":"17","author":"Koita","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2021091709024898400_dkab219-B9","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1128\/AAC.16.6.710","article-title":"Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique","volume":"16","author":"Desjardins","year":"1979","journal-title":"Antimicrob Agents Chemother"},{"key":"2021091709024898400_dkab219-B10","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1128\/AAC.02350-12","article-title":"High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool","volume":"57","author":"Woodrow","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2021091709024898400_dkab219-B11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.actatropica.2011.08.013","article-title":"In vitro Amodiaquine Resistance and its Association with Mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria","volume":"120","author":"Folarin","year":"2011","journal-title":"Acta Trop"},{"key":"2021091709024898400_dkab219-B12","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1128\/AAC.40.8.1846","article-title":"4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant Plasmodium falciparum","volume":"40","author":"Ridley","year":"1996","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/10\/2565\/40394527\/dkab219.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/10\/2565\/40394527\/dkab219.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T09:10:41Z","timestamp":1631869841000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/10\/2565\/6318627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,10]]},"references-count":12,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,7,10]]},"published-print":{"date-parts":[[2021,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab219","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,7,10]]}}}