{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:47:13Z","timestamp":1789667233642,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Esp\u00edrito Santo (FAPES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Leishmaniasis is a group of infectious diseases caused by protozoan parasites that belong to the genus Leishmania. Currently, there is no human vaccine, and the available treatments are associated with toxicity, high cost, and the emergence of resistant strains. These factors highlight the need to identify new antileishmanial candidates. In this study, we synthesized twenty-four methoxylated cinnamides containing 1,2,3-triazole fragments and evaluated their antileishmanial activity against the Leishmania braziliensis species, which is the main etiological agent responsible for American Tegumentary Leishmaniasis (ATL). The cinnamides were synthetically prepared using nucleophilic acyl substitution and copper(I)-catalyzed azide\u2013alkyne cycloaddition (CuAAC) reactions. The compounds were characterized using infrared, nuclear magnetic resonance, and high-resolution mass spectrometry techniques. We performed preliminary studies to evaluate the biological activity of these compounds against L. braziliensis promastigotes and axenic amastigotes. Compound 28, N-((1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-1H-1,2,3-triazole-4-yl) methyl)-3,4-dimethoxy cinnamide, demonstrated relevant antileishmanial activity with low toxicity in murine cells. The selectivity index values for this compound were superior compared with data obtained using amphotericin B. Furthermore, this cinnamide derivative reduced the infection percentage and number of recovered amastigotes in L. braziliensis-infected macrophages. It also induced an increase in reactive oxygen species production, depolarization of the mitochondrial potential, and disruption of the parasite membrane. Taken together, these findings suggest that this synthetic compound holds potential as an antileishmanial candidate and should be considered for future studies in the treatment of ATL.<\/jats:p>","DOI":"10.3390\/ph16081113","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis of 1,2,3-Triazole-Containing Methoxylated Cinnamides and Their Antileishmanial Activity against the Leishmania braziliensis Species"],"prefix":"10.3390","volume":"16","author":[{"given":"Fab\u00edola Suelen dos","family":"Santos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese Org\u00e2nica (LABSINTO), Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossimiriam Pereira de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese Org\u00e2nica (LABSINTO), Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7882-215X","authenticated-orcid":false,"given":"Camila Sim\u00f5es de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora Vasconcelos Costa","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabr\u00edcio Marques de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Instituto Federal de Minas Gerais (IFMG), Campus Ouro Branco, Ouro Branco 36420-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-1141","authenticated-orcid":false,"given":"Luciana Maria Ribeiro","family":"Antinarelli","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-278X","authenticated-orcid":false,"given":"Elaine Soares","family":"Coimbra","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40249-020-0630-9","article-title":"Neglected tropical diseases: An effective global response to local poverty-related disease priorities","volume":"9","author":"Engels","year":"2020","journal-title":"Infect. 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