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The compounds were accessed through a silver\u2010catalyzed three\u2010component reaction of trifluorodiazoethane with <jats:italic>in\u2005situ<\/jats:italic> generated Schiff base from corresponding quinolinylamine and aldehydes. While attempting to incorporate a sulfonyl moiety, the triazoline formed underwent spontaneous oxidative aromatization to afford triazole derivatives. All synthesized compounds were tested for their antimalarial potential <jats:italic>in\u2005vitro<\/jats:italic> and <jats:italic>in\u2005vivo<\/jats:italic>. Out of 32 compounds, four showed the most promising antimalarial activity with IC<jats:sub>50<\/jats:sub> values ranging from 4 to 20\u2005nM against Pf3D7 (chloroquine\u2010sensitive) and from 120 to 450\u2005nM against PfK1 (chloroquine\u2010resistant) strains. One of these compounds was also found to be effective in animal studies; it showed a 99.9\u2009% decrease in parasitic load on day 7 post\u2010infection along with a 40\u2009% cure rate and longest host life span.<\/jats:p>","DOI":"10.1002\/cmdc.202200653","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:15:13Z","timestamp":1678234513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Incorporation of Trifluoromethyltriazoline in the Side Chain of 4\u2010Aminoquinolines: Synthesis and Evaluation as Antiplasmodial Agents"],"prefix":"10.1002","volume":"18","author":[{"given":"Kanchan","family":"Yadav","sequence":"first","affiliation":[{"name":"Molecular Microbiology and Immunology Division CSIR-Central Drug Research Institute Jankipuram Extension  Sitapur Road, P.O. 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