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A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of <jats:italic>N<\/jats:italic>\u2010cinnamoylated quinacrine surrogates, 9\u2010(<jats:italic>N<\/jats:italic>\u2010cinnamoylaminobutyl)\u2010amino\u20106\u2010chloro\u20102\u2010methoxyacridines, is reported. The compounds were found to be highly potent against both blood\u2010stage <jats:italic>P.\u2005falciparum<\/jats:italic>, chloroquine\u2010sensitive 3D7 (IC<jats:sub>50<\/jats:sub>=17.0\u201339.0\u2005n<jats:sc>M<\/jats:sc>) and chloroquine\u2010resistant W2 and Dd2 strains (IC<jats:sub>50<\/jats:sub>=3.2\u201341.2 and 27.1\u2013131.0\u2005n<jats:sc>M<\/jats:sc>, respectively), and liver\u2010stage <jats:italic>P.\u2005berghei<\/jats:italic> (IC<jats:sub>50<\/jats:sub>=1.6\u20134.9\u2005\u03bc<jats:sc>M<\/jats:sc>) parasites. These findings bring new hope for the possible future \u201crise of a fallen angel\u201d in antimalarial chemotherapy, with a potential resurgence of quinacrine\u2010related compounds as dual\u2010stage antimalarial leads.<\/jats:p>","DOI":"10.1002\/cmdc.201300459","type":"journal-article","created":{"date-parts":[[2013,12,27]],"date-time":"2013-12-27T07:56:40Z","timestamp":1388131000000},"page":"305-310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["<i>N\u2010<\/i>Cinnamoylation of Antimalarial Classics: Quinacrine Analogues with Decreased Toxicity and Dual\u2010Stage 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