In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase
<b>Background/Objectives</b>: The anti-<i>Leishmania</i> potential of <i>Curcuma longa</i> and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of <i&...
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2025-06-01
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| author | Flora F. S. Spíndola Anderson S. Pinheiro Maria Athana Mpalantinos Jefferson R. A. Silva Walter S. M. F. Neto Raissa A. Conceição Eduarda M. Barreto Barbara A. Abrahim-Vieira Carlos R. Rodrigues Alessandra M. T. Souza Dirlei Nico Ana Claudia F. Amaral Andreza R. Garcia Igor A. Rodrigues |
| author_facet | Flora F. S. Spíndola Anderson S. Pinheiro Maria Athana Mpalantinos Jefferson R. A. Silva Walter S. M. F. Neto Raissa A. Conceição Eduarda M. Barreto Barbara A. Abrahim-Vieira Carlos R. Rodrigues Alessandra M. T. Souza Dirlei Nico Ana Claudia F. Amaral Andreza R. Garcia Igor A. Rodrigues |
| author_sort | Flora F. S. Spíndola |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: The anti-<i>Leishmania</i> potential of <i>Curcuma longa</i> and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of <i>C. longa</i> extracts and curcumin on <i>Leishmania infantum</i> arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. <b>Methods</b>: 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 <i>L. infantum</i> arginase (<i>Li</i>ARG) was assessed by urea quantification, while molecular docking explored interactions between the main compounds annotated in the extracts and the enzyme’s active site. Biological activity was tested against <i>L. infantum</i> promastigotes, intracellular amastigotes, and mammalian cells. <b>Results</b>: LC-MS and GC-MS revealed curcuminoids and turmerones as main compounds annotated in the extracts. DCCURC, HEXCURC, and curcumin showed the strongest <i>Li</i>ARG inhibition (IC<sub>50</sub> = 10.04, 14.4, and 17.55 μg/mL, respectively). Docking analysis revealed that curcumin, demethoxycurcumin, and bisdemethoxycurcumin bind near the active site, with binding energies of –3.43, –4.14, and –3.99 kcal/mol, respectively. Curcumin demonstrated superior anti-promastigote activity (IC<sub>50</sub> = 15.01 μg/mL) and selectivity (SI = 12.7) compared to the extracts. It also significantly reduced amastigote burden in infected macrophages (IC<sub>50</sub> = 13.6 μg/mL). <b>Conclusions</b>: This is the first report demonstrating that <i>C. longa</i> extracts and curcumin inhibit <i>Li</i>ARG. These findings support curcumin’s potential as a lead compound for developing multi-target therapies against leishmaniasis, combining enzyme inhibition with direct antiparasitic effects. |
| format | Article |
| id | doaj-art-baaa3bebfe3044be94cadb16d40d33f0 |
| institution | Kabale University |
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| publishDate | 2025-06-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-baaa3bebfe3044be94cadb16d40d33f02025-08-20T03:27:32ZengMDPI AGPharmaceuticals1424-82472025-06-0118685110.3390/ph18060851In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> ArginaseFlora F. S. Spíndola0Anderson S. Pinheiro1Maria Athana Mpalantinos2Jefferson R. A. Silva3Walter S. M. F. Neto4Raissa A. Conceição5Eduarda M. Barreto6Barbara A. Abrahim-Vieira7Carlos R. Rodrigues8Alessandra M. T. Souza9Dirlei Nico10Ana Claudia F. Amaral11Andreza R. Garcia12Igor A. Rodrigues13Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLaboratório de Produtos Naturais e Derivados, Farmanguinhos Fiocruz, Manguinhos, Rio de Janeiro 21041-250, RJ, BrazilLaboratório de Cromatografia, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas, Manaus 69077-000, AM, BrazilLaboratório de Cromatografia, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas, Manaus 69077-000, AM, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilDepartamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilLaboratório de Produtos Naturais e Derivados, Farmanguinhos Fiocruz, Manguinhos, Rio de Janeiro 21041-250, RJ, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil<b>Background/Objectives</b>: The anti-<i>Leishmania</i> potential of <i>Curcuma longa</i> and its derivatives, such as curcuminoids, is well-established, yet their mechanisms of action remain underexplored. This study investigates the inhibitory effects of <i>C. longa</i> extracts and curcumin on <i>Leishmania infantum</i> arginase, a key enzyme in polyamine and trypanothione biosynthesis, and evaluates their antiparasitic activity. <b>Methods</b>: 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 <i>L. infantum</i> arginase (<i>Li</i>ARG) was assessed by urea quantification, while molecular docking explored interactions between the main compounds annotated in the extracts and the enzyme’s active site. Biological activity was tested against <i>L. infantum</i> promastigotes, intracellular amastigotes, and mammalian cells. <b>Results</b>: LC-MS and GC-MS revealed curcuminoids and turmerones as main compounds annotated in the extracts. DCCURC, HEXCURC, and curcumin showed the strongest <i>Li</i>ARG inhibition (IC<sub>50</sub> = 10.04, 14.4, and 17.55 μg/mL, respectively). Docking analysis revealed that curcumin, demethoxycurcumin, and bisdemethoxycurcumin bind near the active site, with binding energies of –3.43, –4.14, and –3.99 kcal/mol, respectively. Curcumin demonstrated superior anti-promastigote activity (IC<sub>50</sub> = 15.01 μg/mL) and selectivity (SI = 12.7) compared to the extracts. It also significantly reduced amastigote burden in infected macrophages (IC<sub>50</sub> = 13.6 μg/mL). <b>Conclusions</b>: This is the first report demonstrating that <i>C. longa</i> extracts and curcumin inhibit <i>Li</i>ARG. These findings support curcumin’s potential as a lead compound for developing multi-target therapies against leishmaniasis, combining enzyme inhibition with direct antiparasitic effects.https://www.mdpi.com/1424-8247/18/6/851antileishmanialcurcuminturmeroneADMETmolecular dockingenzymatic inhibition |
| spellingShingle | Flora F. S. Spíndola Anderson S. Pinheiro Maria Athana Mpalantinos Jefferson R. A. Silva Walter S. M. F. Neto Raissa A. Conceição Eduarda M. Barreto Barbara A. Abrahim-Vieira Carlos R. Rodrigues Alessandra M. T. Souza Dirlei Nico Ana Claudia F. Amaral Andreza R. Garcia Igor A. Rodrigues In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase Pharmaceuticals antileishmanial curcumin turmerone ADMET molecular docking enzymatic inhibition |
| title | In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase |
| title_full | In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase |
| title_fullStr | In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase |
| title_full_unstemmed | In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase |
| title_short | In Vitro and In Silico Assessments of Curcuminoids and Turmerones from <i>Curcuma longa</i> as Novel Inhibitors of <i>Leishmania infantum</i> Arginase |
| title_sort | in vitro and in silico assessments of curcuminoids and turmerones from i curcuma longa i as novel inhibitors of i leishmania infantum i arginase |
| topic | antileishmanial curcumin turmerone ADMET molecular docking enzymatic inhibition |
| url | https://www.mdpi.com/1424-8247/18/6/851 |
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