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There are limited treatment options for CL, and the available drugs are becoming less efficacious due to drug resistance. More efficacious and safer antileishmanial drugs are needed. In this study, the biological effect of seven synthetically accessible nitroaromatic compounds was evaluated <jats:italic>in vitro<\/jats:italic> against amastigotes of <jats:italic>Leishmania amazonensis<\/jats:italic>, followed by <jats:italic>in vivo<\/jats:italic> evaluation using mouse models of CL. Two compounds (<jats:bold>6<\/jats:bold> and <jats:bold>7<\/jats:bold>) were active against amastigotes <jats:italic>in vitro<\/jats:italic> [half-maximal effective concentration (EC<jats:sub>50<\/jats:sub>): 4.57 \u00b1 0.08 and 9.19 \u00b1 0.68 <jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>, respectively], with selectivity indexes &gt;50, and the other compounds were not selective. <jats:italic>In vivo<\/jats:italic>, compounds <jats:bold>6<\/jats:bold> and <jats:bold>7<\/jats:bold> (10 mg kg<jats:sup>\u22121<\/jats:sup>, twice a day for 14 days) failed to reduce skin lesion sizes and parasite loads determined by light microscopy of lesion <jats:italic>imprints<\/jats:italic> and quantitative polymerase chain reaction. Nevertheless, the <jats:italic>in vitro<\/jats:italic> leishmanicidal efficacy sustained their use as templates for nitroimidazole-based antileishmanial drug discovery programmes focusing on analogues with more suitable properties.<\/jats:p>","DOI":"10.1017\/s0031182021002079","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T09:37:35Z","timestamp":1643881055000},"page":"490-495","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":11,"title":["Phenotypic investigation of 4-nitrophenylacetyl- and 4-nitro-1<i>H<\/i>-imidazoyl-based compounds as antileishmanial agents"],"prefix":"10.1017","volume":"149","author":[{"given":"Camila C.","family":"Santos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaisheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos M.","family":"Batista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel M.","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly C.","family":"Demarque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nat\u00e1lia L.","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otac\u00edlio C.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ifedayo Victor","family":"Ogungbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-6106","authenticated-orcid":false,"given":"Maria de Nazar\u00e9 Correia","family":"Soeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"S0031182021002079_ref24","doi-asserted-by":"publisher","DOI":"10.1353\/bhm.2006.0046"},{"key":"S0031182021002079_ref12","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761994000300027"},{"key":"S0031182021002079_ref9","doi-asserted-by":"publisher","DOI":"10.1021\/jm701122q"},{"key":"S0031182021002079_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5769(99)00020-3"},{"key":"S0031182021002079_ref21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02205-17"},{"key":"S0031182021002079_ref22","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01188-20"},{"key":"S0031182021002079_ref26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005971"},{"key":"S0031182021002079_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.03.039"},{"key":"S0031182021002079_ref13","doi-asserted-by":"publisher","DOI":"10.1590\/abd1806-4841.20142226"},{"key":"S0031182021002079_ref17","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00104"},{"key":"S0031182021002079_ref19","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762010000200022"},{"key":"S0031182021002079_ref2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"S0031182021002079_ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-015-0114-z"},{"key":"S0031182021002079_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.11.008"},{"key":"S0031182021002079_ref23","first-page":"129","article-title":"Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis","volume":"11","author":"Van Bocxlaer","year":"2019","journal-title":"International Journal for Parasitology: Drugs and Drug Resistance"},{"key":"S0031182021002079_ref11","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4683"},{"key":"S0031182021002079_ref4","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182020001900"},{"key":"S0031182021002079_ref15","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00499"},{"key":"S0031182021002079_ref16","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.15-0408"},{"key":"S0031182021002079_ref20","first-page":"538629","article-title":"Mucocutaneous leishmaniasis: knowledge, attitudes, and practices among Paraguayan communities, patients, and health professionals","author":"Ruoti","year":"2013","journal-title":"Journal of Tropical Medicine"},{"key":"S0031182021002079_ref7","unstructured":"Drugs for Neglected Diseases Initiative (2020) Target product profile for cutaneous leishmaniasis. 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