{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:28:27Z","timestamp":1778743707781,"version":"3.51.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Leishmaniasis affects mainly low-income populations in tropical regions. Radical innovation in drug discovery is time-consuming and expensive, imposing severe restrictions on the ability to launch new chemical entities for the treatment of neglected diseases. Drug repositioning is an attractive strategy for addressing a specific demand more easily. In this project, we have evaluated the antileishmanial activities of 30 drugs currently in clinical use for various morbidities. Ezetimibe, clinically used to reduce intestinal cholesterol absorption in dyslipidemic patients, killed\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania amazonensis<\/jats:named-content>\n            promastigotes with a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) of 30 \u03bcM. Morphological analysis revealed that ezetimibe caused the parasites to become rounded, with multiple nuclei and flagella. Analysis by gas chromatography (GC)-mass spectrometry (MS) showed that promastigotes treated with ezetimibe had smaller amounts of C-14-demethylated sterols, and accumulated more cholesterol and lanosterol, than untreated promastigotes. We then evaluated the combination of ezetimibe with well-known antileishmanial azoles. The fractional inhibitory concentration index (FICI) indicated synergy when ezetimibe was combined with ketoconazole or miconazole. The activity of ezetimibe against intracellular amastigotes was confirmed, with an IC\n            <jats:sub>50<\/jats:sub>\n            of 20 \u03bcM, and ezetimibe reduced the IC\n            <jats:sub>90<\/jats:sub>\n            s of ketoconazole and miconazole from 11.3 and 11.5 \u03bcM to 4.14 and 8.25 \u03bcM, respectively. Subsequently, we confirmed the activity of ezetimibe\n            <jats:italic>in vivo<\/jats:italic>\n            , showing that it decreased lesion development and parasite loads in murine cutaneous leishmaniasis. We concluded that ezetimibe has promising antileishmanial activity and should be considered in combination with azoles in further preclinical and clinical studies.\n          <\/jats:p>","DOI":"10.1128\/aac.01545-16","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T03:03:57Z","timestamp":1473217437000},"page":"6844-6852","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Antileishmanial Activity of Ezetimibe: Inhibition of Sterol Biosynthesis,\n            <i>In Vitro<\/i>\n            Synergy with Azoles, and Efficacy in Experimental Cutaneous Leishmaniasis"],"prefix":"10.1128","volume":"60","author":[{"given":"Valter Viana","family":"Andrade-Neto","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed\u00e9zio Ferreira","family":"Cunha-J\u00fanior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilene Marcuzzo do","family":"Canto-Cavalheiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ge\u00f3rgia Correa","family":"Atella","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Talita de Almeida","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Bioorg\u00e2nica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo Roberto Ribeiro","family":"Costa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Bioorg\u00e2nica, Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2240-4519","authenticated-orcid":false,"given":"Eduardo Caio","family":"Torres-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.09.014"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3855\/jidc.6833"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_3_3_5_2","first-page":"36","article-title":"Comunica\u00e7\u00e3o \u00e0 Sess\u00e3o de 24 de abril de 1912 da Sociedade Brasileira de Dermatologia","volume":"1","author":"Vianna G","year":"1912","unstructured":"Vianna G. 1912. Comunica\u00e7\u00e3o \u00e0 Sess\u00e3o de 24 de abril de 1912 da Sociedade Brasileira de Dermatologia. Arch Bras Med 1:36\u201338.","journal-title":"Arch Bras Med"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2011.02.007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.11845"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.99326"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit102"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01023-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135556"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2013-001700"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2014.02.002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg301"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1139\/o59-099"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn546"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2007.09.014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.07.011"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1995.tb01591.x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-015-4618-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.07.012"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(86)90145-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(84)90039-2"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(89)90026-1"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2013.37.4.240"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(88)90166-1"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12359"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.2.487-499.2002"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083247"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-013-3274-x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90347-L"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01150-15"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/09546630152607899"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.1.172"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01545-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01545-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:33:23Z","timestamp":1645475603000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01545-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1128\/AAC.01545-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01545-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11]]},"assertion":[{"value":"2016-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}