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This study investigates the inhibitory effects of C. longa extracts and curcumin on Leishmania infantum arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. Methods: Extracts were prepared via rhizome successive maceration with hexane (HEXCURC), dichloromethane (DCCURC), and ethanol (ETOHCURC) and chemically characterized by a combination of chromatographic and spectrometric methods. The inhibition of recombinant L. infantum arginase (LiARG) was assessed by urea quantification, while molecular docking explored interactions between the main compounds annotated in the extracts and the enzyme\u2019s active site. Biological activity was tested against L. infantum promastigotes, intracellular amastigotes, and mammalian cells. Results: LC-MS and GC-MS revealed curcuminoids and turmerones as main compounds annotated in the extracts. DCCURC, HEXCURC, and curcumin showed the strongest LiARG inhibition (IC50 = 10.04, 14.4, and 17.55 \u03bcg\/mL, respectively). Docking analysis revealed that curcumin, demethoxycurcumin, and bisdemethoxycurcumin bind near the active site, with binding energies of \u20133.43, \u20134.14, and \u20133.99 kcal\/mol, respectively. Curcumin demonstrated superior anti-promastigote activity (IC50 = 15.01 \u03bcg\/mL) and selectivity (SI = 12.7) compared to the extracts. It also significantly reduced amastigote burden in infected macrophages (IC50 = 13.6 \u03bcg\/mL). Conclusions: This is the first report demonstrating that C. longa extracts and curcumin inhibit LiARG. These findings support curcumin\u2019s potential as a lead compound for developing multi-target therapies against leishmaniasis, combining enzyme inhibition with direct antiparasitic effects.<\/jats:p>","DOI":"10.3390\/ph18060851","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:43:14Z","timestamp":1749202994000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro and In Silico Assessments of Curcuminoids and Turmerones from Curcuma longa as Novel Inhibitors of Leishmania infantum Arginase"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7234-032X","authenticated-orcid":false,"given":"Flora F. S.","family":"Sp\u00edndola","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-6931","authenticated-orcid":false,"given":"Anderson S.","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Instituto de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Athana","family":"Mpalantinos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais e Derivados, Farmanguinhos Fiocruz, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson R. A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cromatografia, Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal do Amazonas, Manaus 69077-000, AM, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter S. M. F.","family":"Neto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cromatografia, Departamento de Qu\u00edmica, Instituto de Ci\u00eancias Exatas, Universidade Federal do Amazonas, Manaus 69077-000, AM, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-7673","authenticated-orcid":false,"given":"Raissa A.","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Departamento de F\u00e1rmacos e Medicamentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduarda M.","family":"Barreto","sequence":"additional","affiliation":[{"name":"Departamento de F\u00e1rmacos e Medicamentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Abrahim-Vieira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Departamento de F\u00e1rmacos e Medicamentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos R.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Departamento de F\u00e1rmacos e Medicamentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9986-405X","authenticated-orcid":false,"given":"Alessandra M. T.","family":"Souza","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Departamento de F\u00e1rmacos e Medicamentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirlei","family":"Nico","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia F.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Produtos Naturais e Derivados, Farmanguinhos Fiocruz, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreza R.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-3991","authenticated-orcid":false,"given":"Igor A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"},{"name":"Departamento de Produtos Naturais e Alimentos, Faculdade de Farm\u00e1cia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","unstructured":"WHO, World Health Organization (2025, February 26). 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