{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T13:24:03Z","timestamp":1762608243028,"version":"3.40.5"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ACT\u2019s low levels of <jats:italic>Plasmodium<\/jats:italic> parasitemia clearance are worrisome since it is the last treatment option against <jats:italic>P. falciparum<\/jats:italic>. This scenario has led to investigations of compounds with different mechanisms of action for malaria treatment. Natural compounds like ursolic acid (UA) and betulinic acid (BA), distinguished by their activity against numerous microorganisms, including <jats:italic>P. falciparum<\/jats:italic>, have become relevant. This study evaluated the antiplasmodial activity of imidazole derivatives of UA and BA against <jats:italic>P. falciparum<\/jats:italic> in vitro. Eight molecules were obtained by semisynthesis and tested against <jats:italic>P. falciparum<\/jats:italic> strains (NF54 and CQ\u2010resistant 106\/cand isolated in Porto Velho, Brazil); <jats:bold>2a<\/jats:bold> and <jats:bold>2b<\/jats:bold> showed activity against NF54 and 106\/cand strains with IC<jats:sub>50<\/jats:sub>\u00a0&lt;\u00a010\u00a0\u00b5M. They presented high selectivity indexes (SI\u00a0&gt;\u00a025) and showed synergism when combined with artemisinin. <jats:bold>2b<\/jats:bold> inhibited the parasite's ring and schizont forms regardless of when the treatment began. In silico analysis presented a tight bind of <jats:bold>2b<\/jats:bold> in the topoisomerase II\u2010DNA complex. This study demonstrates the importance of natural derivate compounds as new candidates for malarial treatment with new mechanisms of action. Semisynthesis led to new triterpenes that are active against <jats:italic>P. falciparum<\/jats:italic> and may represent new alternatives for malaria drug development.<\/jats:p>","DOI":"10.1111\/cbdd.13835","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T16:27:03Z","timestamp":1614443223000},"page":"1038-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ursolic and betulinic semisynthetic derivatives show activity against CQ\u2010resistant <i>Plasmodium falciparum<\/i> isolated from Amazonia"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-4638","authenticated-orcid":false,"given":"Daniel","family":"Sol Sol de Medeiros","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Experimental Porto Velho Brasil"},{"name":"Plataforma de Bioensaios em Mal\u00e1ria e Leishmaniose \u2013 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