{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:27:11Z","timestamp":1768966031276,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T00:00:00Z","timestamp":1662768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian Agency Conselho National de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Eight gallic acid alkyl esters (1\u20138) were synthesized via Fischer esterification and evaluated for their trypanocidal and leishmanicidal activity using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. The general cytotoxicity of the esters was evaluated with human HL-60 cells. The compounds displayed moderate to good trypanocidal but zero to low leishmanicidal activity. Gallic acid esters with alkyl chains of three or four carbon atoms in linear arrangement (propyl (4), butyl (5), and isopentyl (6)) were found to be the most trypanocidal compounds with 50% growth inhibition values of ~3 \u03bcM. On the other hand, HL-60 cells were less susceptible to the compounds, thus, resulting in moderate selectivity indices (ratio of cytotoxic to trypanocidal activity) of &gt;20 for the esters 4\u20136. Modeling studies combining molecular docking and molecular dynamics simulations suggest that the trypanocidal mechanism of action of gallic acid alkyl esters could be related to the inhibition of the T. brucei alternative oxidase. This suggestion is supported by the observation that trypanosomes became immobile within minutes when incubated with the esters in the presence of glycerol as the sole substrate. These results indicate that gallic acid alkyl esters are interesting compounds to be considered for further antitrypanosomal drug development.<\/jats:p>","DOI":"10.3390\/molecules27185876","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T01:44:03Z","timestamp":1663033443000},"page":"5876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gallic Acid Alkyl Esters: Trypanocidal and Leishmanicidal Activity, and Target Identification via Modeling Studies"],"prefix":"10.3390","volume":"27","author":[{"given":"Dietmar","family":"Steverding","sequence":"first","affiliation":[{"name":"Bob Champion Research and Education Building, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1zaro Gomes","family":"do Nascimento","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-0035","authenticated-orcid":false,"given":"Yunierkis","family":"Perez-Castillo","sequence":"additional","affiliation":[{"name":"Bio-Cheminformatics Research Group, Universidad de Las Am\u00e9ricas, Quito 170516, Ecuador"},{"name":"Facultad de Ingenier\u00eda y Ciencias Aplicadas, \u00c1rea de Ciencias Aplicadas, Universidad de Las Am\u00e9ricas, Quito 170516, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7180-4896","authenticated-orcid":false,"given":"Dami\u00e3o Pergentino","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, PB, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1756-3305-1-3","article-title":"The history of African trypanosomiasis","volume":"1","author":"Steverding","year":"2008","journal-title":"Parasit. 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