{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:23:10Z","timestamp":1768342990692,"version":"3.49.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n New drugs to treat malaria must act rapidly and be highly potent against asexual blood stages, well tolerated, and affordable to residents of regions of endemicity. This was the case with chloroquine (CQ), a 4-aminoquinoline drug used for the prevention and treatment of malaria. However, since the 1960s,\n Plasmodium falciparum<\/jats:named-content>\n resistance to this drug has spread globally, and more recently, emerging resistance to CQ by\n Plasmodium vivax<\/jats:named-content>\n threatens the health of 70 to 320 million people annually. Despite the emergence of CQ resistance, synthetic quinoline derivatives remain validated leads for new drug discovery, especially if they are effective against CQ-resistant strains of malaria. In this study, we investigated the activities of two novel 4-aminoquinoline derivatives, TDR 58845,\n N<\/jats:italic>\n 1<\/jats:sup>\n -(7-chloro-quinolin-4-yl)-2-methyl-propane-1,2-diamine, and TDR 58846,\n N<\/jats:italic>\n 1<\/jats:sup>\n -(7-chloro-quinolin-4-yl)-2,\n N<\/jats:italic>\n 2<\/jats:sup>\n ,\n N<\/jats:italic>\n 2<\/jats:sup>\n -trimethylpropane-1,2-diamine and found them to be active against\n P. falciparum<\/jats:named-content>\n in vitro<\/jats:italic>\n and\n Plasmodium berghei<\/jats:named-content>\n in vivo<\/jats:italic>\n . The\n P. falciparum<\/jats:named-content>\n clones and isolates tested were susceptible to TDR 58845 and TDR 58846 (50% inhibitory concentrations [IC\n 50<\/jats:sub>\n s] ranging from 5.52 to 89.8 nM), including the CQ-resistant reference clone W2 and two multidrug-resistant parasites recently isolated from Thailand and Cambodia. Moreover, these 4-aminoquinolines were active against early and late\n P. falciparum<\/jats:named-content>\n gametocyte stages and cured BALB\/c mice infected with\n P. berghei<\/jats:named-content>\n . TDR 58845 and TDR 58846 at 40 mg\/kg were sufficient to cure mice, and total doses of 480 mg\/kg of body weight were well tolerated. Our findings suggest these novel 4-aminoquinolines should be considered for development as potent antimalarials that can be used in combination to treat multidrug-resistant\n P. falciparum<\/jats:named-content>\n and\n P. vivax<\/jats:named-content>\n .\n <\/jats:p>","DOI":"10.1128\/aac.01061-12","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T03:51:19Z","timestamp":1340077879000},"page":"4685-4692","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Novel 4-Aminoquinoline Analogs Highly Active against the Blood and Sexual Stages of Plasmodium\n In Vivo<\/i>\n and\n In Vitro<\/i>"],"prefix":"10.1128","volume":"56","author":[{"given":"Fabi\u00e1n E.","family":"S\u00e1enz","sequence":"first","affiliation":[{"name":"Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Mutka","sequence":"additional","affiliation":[{"name":"Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Udenze","sequence":"additional","affiliation":[{"name":"Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayoade M. 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