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Chemically, quinolines are excellent ligands for metal coordination and are deployed as drugs for malaria treatment. There is a growing body of evidence indicating that metal complexes can be conjugated with antimalarial quinolines to be used as chemical tools to overcome the disadvantages of quinolines, improving their bioactive speciation, cellular distribution, and subsequently broadening the spectrum of activity to multiple stages of the complex <jats:italic>Plasmodium<\/jats:italic> life cycle. In this study, four novel complexes of ruthenium(II)\u2010 and gold(I)\u2010containing amodiaquine (AQ) were synthesized, and a careful chemical characterization revealed the precise coordination site of AQ to the metals. Their speciation in solution was investigated, demonstrating the stability of the quinoline\u2010metal bond. Ru<jats:sup>II<\/jats:sup>\u2010 and Au<jats:sup>I<\/jats:sup>\u2010AQ complexes were demonstrated to be potent and efficacious in inhibiting parasite growth in multiple stages of the <jats:italic>Plasmodium<\/jats:italic> life cycle as assayed in\u2005vitro and in\u2005vivo. These properties could be attributed to the ability of the metal\u2010AQ complexes to reproduce the suppression of heme detoxification induced by AQ, while also inhibiting other processes in the parasite life cycle; this can be attributed to the action of the metallic species. Altogether, these findings indicate that metal coordination with antimalarial quinolines is a potential chemical tool for drug design and discovery in malaria and other infectious diseases susceptible to quinoline treatment.<\/jats:p>","DOI":"10.1002\/chem.202301642","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T08:42:50Z","timestamp":1688978570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antimalarial Agents Derived from Metal\u2010Amodiaquine Complexes with Activity in Multiple Stages of the <i>Plasmodium<\/i> Life Cycle"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-5544","authenticated-orcid":false,"given":"Legna","family":"Colina\u2010Vegas","sequence":"first","affiliation":[{"name":"Instituto de Qu\u00edmica Universidade Federal do Rio Grande do Sul  Porto Alegre CP 91501\u2013970, RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-7542","authenticated-orcid":false,"given":"Mariana","family":"da Cruz B. 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