Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i>
<i>Leishmania infantum</i> is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. <i>L. infantum</i> is transmitted by female phlebotomine...
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/6/2844 |
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| author | Mayara Castro de Morais Gisele Alves Medeiros Fernanda Silva Almeida Juliana da Câmara Rocha Yunierkis Perez-Castillo Tatjana de Souza Lima Keesen Damião Pergentino de Sousa |
| author_facet | Mayara Castro de Morais Gisele Alves Medeiros Fernanda Silva Almeida Juliana da Câmara Rocha Yunierkis Perez-Castillo Tatjana de Souza Lima Keesen Damião Pergentino de Sousa |
| author_sort | Mayara Castro de Morais |
| collection | DOAJ |
| description | <i>Leishmania infantum</i> is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. <i>L. infantum</i> is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against <i>L. infantum</i> is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound <b>32</b> (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC<sub>50</sub> = 33.71 μM) with the highest selectivity index (SI > 42.46), followed by compound <b>15</b> (piperonyl cinnamate) with an IC<sub>50</sub> = 42.80 μM and SI > 32.86. Compound <b>32</b> was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in <i>L. infantum</i> was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against <i>Leishmania</i> species. |
| first_indexed | 2024-03-11T06:06:49Z |
| format | Article |
| id | doaj.art-dce3613366804372aa47e382ee58c441 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T06:06:49Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-dce3613366804372aa47e382ee58c4412023-11-17T12:55:57ZengMDPI AGMolecules1420-30492023-03-01286284410.3390/molecules28062844Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i>Mayara Castro de Morais0Gisele Alves Medeiros1Fernanda Silva Almeida2Juliana da Câmara Rocha3Yunierkis Perez-Castillo4Tatjana de Souza Lima Keesen5Damião Pergentino de Sousa6Department of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, BrazilDepartment of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, BrazilImmunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, BrazilImmunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, BrazilBio-Cheminformatics Research Group and Area de Ciencias Aplicadas, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, Quito 170503, EcuadorImmunology of Infectious Diseases Laboratory, Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa 58051-900, BP, BrazilDepartment of Pharmaceutical Sciences, Federal University of Paraíba, João Pessoa 58051-900, BP, Brazil<i>Leishmania infantum</i> is the etiological agent of visceral leishmaniasis (VL) in South America, the Mediterranean basin, and West and Central Asia. The most affected country, Brazil, reported 4297 VL cases in 2017. <i>L. infantum</i> is transmitted by female phlebotomine sand flies during successive blood meals. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new antileishmanial drugs. Cinnamic acid derivatives have shown several pharmacological activities, including antiparasitic action. Therefore, in the present study, the biological evaluation of cinnamic acid and thirty-four derivatives against <i>L. infantum</i> is reported. The compounds were prepared by several synthesis methods and characterized by spectroscopic techniques and high-resolution mass spectrometry. The results revealed that compound <b>32</b> (N-(4-isopropylbenzyl)cinnamamide) was the most potent antileishmanial agent (IC<sub>50</sub> = 33.71 μM) with the highest selectivity index (SI > 42.46), followed by compound <b>15</b> (piperonyl cinnamate) with an IC<sub>50</sub> = 42.80 μM and SI > 32.86. Compound <b>32</b> was slightly less potent and nineteen times more selective for the parasite than amphotericin B (MIC = 3.14 uM; SI = 2.24). In the molecular docking study, the most likely target for the compound in <i>L. infantum</i> was aspartyl aminopeptidase, followed by aldehyde dehydrogenase, mitochondrial. The data obtained show the antileishmanial potential of this class of compounds and may be used in the search for new drug candidates against <i>Leishmania</i> species.https://www.mdpi.com/1420-3049/28/6/2844cinnamatecinnamamidenatural productmedicinal plantantiparasitic activity |
| spellingShingle | Mayara Castro de Morais Gisele Alves Medeiros Fernanda Silva Almeida Juliana da Câmara Rocha Yunierkis Perez-Castillo Tatjana de Souza Lima Keesen Damião Pergentino de Sousa Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> Molecules cinnamate cinnamamide natural product medicinal plant antiparasitic activity |
| title | Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> |
| title_full | Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> |
| title_fullStr | Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> |
| title_full_unstemmed | Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> |
| title_short | Antileishmanial Activity of Cinnamic Acid Derivatives against <i>Leishmania infantum</i> |
| title_sort | antileishmanial activity of cinnamic acid derivatives against i leishmania infantum i |
| topic | cinnamate cinnamamide natural product medicinal plant antiparasitic activity |
| url | https://www.mdpi.com/1420-3049/28/6/2844 |
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