Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances
Inhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy. We evaluated the inhibitory potential of selected naturally occurring phenolic substances on Leishmania infantum arginase (ARGLi) and investigated their an...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1616182 |
| _version_ | 1828436620135628800 |
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| author | Andreza R. Garcia Danielle M. P. Oliveira Ana Claudia F. Amaral Jéssica B. Jesus Ana Carolina Rennó Sodero Alessandra M. T. Souza Claudiu T. Supuran Alane B. Vermelho Igor A. Rodrigues Anderson S. Pinheiro |
| author_facet | Andreza R. Garcia Danielle M. P. Oliveira Ana Claudia F. Amaral Jéssica B. Jesus Ana Carolina Rennó Sodero Alessandra M. T. Souza Claudiu T. Supuran Alane B. Vermelho Igor A. Rodrigues Anderson S. Pinheiro |
| author_sort | Andreza R. Garcia |
| collection | DOAJ |
| description | Inhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy. We evaluated the inhibitory potential of selected naturally occurring phenolic substances on Leishmania infantum arginase (ARGLi) and investigated their antileishmanial activity in vivo. ARGLi exhibited a Vmax of 0.28 ± 0.016 mM/min and a Km of 5.1 ± 1.1 mM for L-arginine. The phenylpropanoids rosmarinic acid and caffeic acid (100 µM) showed percentages of inhibition of 71.48 ± 0.85% and 56.98 ± 5.51%, respectively. Moreover, rosmarinic acid and caffeic acid displayed the greatest effects against L. infantum with IC50 values of 57.3 ± 2.65 and 60.8 ± 11 μM for promastigotes, and 7.9 ± 1.7 and 21.9 ± 5.0 µM for intracellular amastigotes, respectively. Only caffeic acid significantly increased nitric oxide production by infected macrophages. Altogether, our results broaden the current spectrum of known arginase inhibitors and revealed promising drug candidates for the therapy of visceral leishmaniasis. |
| first_indexed | 2024-12-10T19:30:33Z |
| format | Article |
| id | doaj.art-bac4db29ff844b0db8ebca4f524359e4 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-10T19:30:33Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-bac4db29ff844b0db8ebca4f524359e42022-12-22T01:36:16ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-013411100110910.1080/14756366.2019.16161821616182Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substancesAndreza R. Garcia0Danielle M. P. Oliveira1Ana Claudia F. Amaral2Jéssica B. Jesus3Ana Carolina Rennó Sodero4Alessandra M. T. Souza5Claudiu T. Supuran6Alane B. Vermelho7Igor A. Rodrigues8Anderson S. Pinheiro9School of Pharmacy, Federal University of Rio de JaneiroInstitute of Chemistry, Federal University of Rio de JaneiroFarmanguinhos, FIOCRUZSchool of Pharmacy, Federal University of Rio de JaneiroSchool of Pharmacy, Federal University of Rio de JaneiroSchool of Pharmacy, Federal University of Rio de JaneiroUniversità degli Studi di Firenze, Sezione di Scienze FarmaceuticheInstitute of Microbiology Paulo de Goes, Federal University of Rio de JaneiroSchool of Pharmacy, Federal University of Rio de JaneiroInstitute of Chemistry, Federal University of Rio de JaneiroInhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy. We evaluated the inhibitory potential of selected naturally occurring phenolic substances on Leishmania infantum arginase (ARGLi) and investigated their antileishmanial activity in vivo. ARGLi exhibited a Vmax of 0.28 ± 0.016 mM/min and a Km of 5.1 ± 1.1 mM for L-arginine. The phenylpropanoids rosmarinic acid and caffeic acid (100 µM) showed percentages of inhibition of 71.48 ± 0.85% and 56.98 ± 5.51%, respectively. Moreover, rosmarinic acid and caffeic acid displayed the greatest effects against L. infantum with IC50 values of 57.3 ± 2.65 and 60.8 ± 11 μM for promastigotes, and 7.9 ± 1.7 and 21.9 ± 5.0 µM for intracellular amastigotes, respectively. Only caffeic acid significantly increased nitric oxide production by infected macrophages. Altogether, our results broaden the current spectrum of known arginase inhibitors and revealed promising drug candidates for the therapy of visceral leishmaniasis.http://dx.doi.org/10.1080/14756366.2019.1616182leishmania infantumvisceral leishmaniasisarginaseinhibitorrosmarinic acidcaffeic acid |
| spellingShingle | Andreza R. Garcia Danielle M. P. Oliveira Ana Claudia F. Amaral Jéssica B. Jesus Ana Carolina Rennó Sodero Alessandra M. T. Souza Claudiu T. Supuran Alane B. Vermelho Igor A. Rodrigues Anderson S. Pinheiro Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances Journal of Enzyme Inhibition and Medicinal Chemistry leishmania infantum visceral leishmaniasis arginase inhibitor rosmarinic acid caffeic acid |
| title | Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances |
| title_full | Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances |
| title_fullStr | Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances |
| title_full_unstemmed | Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances |
| title_short | Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances |
| title_sort | leishmania infantum arginase biochemical characterization and inhibition by naturally occurring phenolic substances |
| topic | leishmania infantum visceral leishmaniasis arginase inhibitor rosmarinic acid caffeic acid |
| url | http://dx.doi.org/10.1080/14756366.2019.1616182 |
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