{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:30:13Z","timestamp":1791639013643,"version":"4.3.4"},"reference-count":49,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda&amp;#x00E7;&amp;#x00E3;o de Amparo &amp;#x00E0; Pesquisa do Estado de S&amp;#x00E3;o Paulo","award":["#19\/23769-4"],"award-info":[{"award-number":["#19\/23769-4"]}]},{"name":"Funda&amp;#x00E7;&amp;#x00E3;o de Amparo &amp;#x00E0; Pesquisa do Estado de S&amp;#x00E3;o Paulo","award":["#17\/06917-4"],"award-info":[{"award-number":["#17\/06917-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Caffeic acid and related natural compounds were previously described as Leishmania amazonensis arginase (L-ARG) inhibitors, and against the whole parasite in vitro. In this study, we tested cinnamides that were previously synthesized to target human arginase. The compound caffeic acid phenethyl amide (CAPA), a weak inhibitor of human arginase (IC50 = 60.3 \u00b1 7.8 \u03bcM) was found to have 9-fold more potency against L-ARG (IC50 = 6.9 \u00b1 0.7 \u03bcM). The other compounds that did not inhibit human arginase were characterized as L-ARG, showing an IC50 between 1.3\u201317.8 \u03bcM, and where the most active was compound 15 (IC50 = 1.3 \u00b1 0.1 \u03bcM). All compounds were also tested against L. amazonensis promastigotes, and only the compound CAPA showed an inhibitory activity (IC50 = 80 \u03bcM). In addition, in an attempt to gain an insight into the mechanism of competitive L-ARG inhibitors, and their selectivity over mammalian enzymes, we performed an extensive computational investigation, to provide the basis for the selective inhibition of L-ARG for this series of compounds. In conclusion, our results indicated that the compounds based on cinnamoyl or 3,4-hydroxy cinnamoyl moiety could be a promising starting point for the design of potential antileishmanial drugs based on selective L-ARG inhibitors.<\/jats:p>","DOI":"10.3390\/molecules25225271","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T20:17:52Z","timestamp":1605212272000},"page":"5271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cinnamides Target Leishmania amazonensis Arginase Selectively"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6246-4404","authenticated-orcid":false,"given":"Edson Roberto","family":"da Silva","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia e Bioqu\u00edmica (LFBq), Departamento de Medicina Veterin\u00e1ria, Universidade de S\u00e3o Paulo Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, SP 13635-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falio Abel Alfredo dos Santos Simone","family":"Come","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia e Bioqu\u00edmica (LFBq), Departamento de Medicina Veterin\u00e1ria, Universidade de S\u00e3o Paulo Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, SP 13635-900, Brazil"},{"name":"Departamento de Pr\u00e9-Cl\u00ednicas, Universidade Eduardo Mondlane, Faculdade de Veterin\u00e1ria, Av. de Mo\u00e7ambique, Km 1.5, Maputo CP 257, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-6242","authenticated-orcid":false,"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Chemi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry, and Pharmacy, DoE Department of Excellence 2018\u20132022 Universit\u00e0 degli Studi di Siena via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Campiani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry, and Pharmacy, DoE Department of Excellence 2018\u20132022 Universit\u00e0 degli Studi di Siena via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tr\u00edcia Maria Ferrreira de Sousa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia e Bioqu\u00edmica (LFBq), Departamento de Medicina Veterin\u00e1ria, Universidade de S\u00e3o Paulo Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, SP 13635-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-5806","authenticated-orcid":false,"given":"Thanh-Nhat","family":"Pham","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, University Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-0253","authenticated-orcid":false,"given":"Marc","family":"Pudlo","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, University Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5116-1395","authenticated-orcid":false,"given":"Corine","family":"Girard","sequence":"additional","affiliation":[{"name":"PEPITE EA4267, University Bourgogne Franche-Comt\u00e9, F-25000 Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia do Carmo","family":"Maquiaveli","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia e Bioqu\u00edmica (LFBq), Departamento de Medicina Veterin\u00e1ria, Universidade de S\u00e3o Paulo Faculdade de Zootecnia e Engenharia de Alimentos, Pirassununga, SP 13635-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"ref_1","unstructured":"WHO (2019, January 25). 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