Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins
Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite an...
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| Format: | Article |
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MDPI AG
2019-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/7/1299 |
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| author | Tanira Matutino Bastos Helena Mannochio Russo Nilmar Silvio Moretti Sergio Schenkman Laurence Marcourt Mahabir Prashad Gupta Jean-Luc Wolfender Emerson Ferreira Queiroz Milena Botelho Pereira Soares |
| author_facet | Tanira Matutino Bastos Helena Mannochio Russo Nilmar Silvio Moretti Sergio Schenkman Laurence Marcourt Mahabir Prashad Gupta Jean-Luc Wolfender Emerson Ferreira Queiroz Milena Botelho Pereira Soares |
| author_sort | Tanira Matutino Bastos |
| collection | DOAJ |
| description | Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator 2 (Sir2) enzymes, or sirtuins, have emerged as attractive targets for the development of novel antitrypanosomatid agents. In the present work, we evaluated the inhibitory effect of natural compounds isolated from cashew nut (<i>Anacardium occidentale</i>, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (<b>1</b>, <b>2</b>), cardanol (<b>3</b>, <b>4</b>), and anacardic acid (<b>5</b>, <b>6</b>) were investigated. The two anacardic acids (<b>5</b>, <b>6</b>) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (<b>2</b>) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (<b>2</b>), with an EC<sub>50</sub> value of 12.25 µM, similar to that of benznidazole. Additionally, compounds (<b>1</b>, <b>4</b>), which were inactive against the sirtuin targets, presented anti-<i>T. cruzi</i> effects. In conclusion, our results showed the potential of <i>Anacardium occidentale</i> compounds for the development of potential sirtuin inhibitors and anti-<i>Trypanosoma cruzi</i> agents. |
| first_indexed | 2024-12-22T19:14:04Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T19:14:04Z |
| publishDate | 2019-04-01 |
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| spelling | doaj.art-e7f420409bc748ba9ebc7ed5cb107de82022-12-21T18:15:34ZengMDPI AGMolecules1420-30492019-04-01247129910.3390/molecules24071299molecules24071299Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> SirtuinsTanira Matutino Bastos0Helena Mannochio Russo1Nilmar Silvio Moretti2Sergio Schenkman3Laurence Marcourt4Mahabir Prashad Gupta5Jean-Luc Wolfender6Emerson Ferreira Queiroz7Milena Botelho Pereira Soares8Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, BrazilSchool of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, SwitzerlandDepartmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, BrazilDepartmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, BrazilSchool of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, SwitzerlandCenter for Pharmacognostic Research on Panamanian Flora (CIFLORPAN), College of Pharmacy, University of Panama, Panama 0824-00172, PanamaSchool of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, SwitzerlandSchool of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, SwitzerlandInstituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, BrazilBenznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator 2 (Sir2) enzymes, or sirtuins, have emerged as attractive targets for the development of novel antitrypanosomatid agents. In the present work, we evaluated the inhibitory effect of natural compounds isolated from cashew nut (<i>Anacardium occidentale</i>, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (<b>1</b>, <b>2</b>), cardanol (<b>3</b>, <b>4</b>), and anacardic acid (<b>5</b>, <b>6</b>) were investigated. The two anacardic acids (<b>5</b>, <b>6</b>) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (<b>2</b>) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (<b>2</b>), with an EC<sub>50</sub> value of 12.25 µM, similar to that of benznidazole. Additionally, compounds (<b>1</b>, <b>4</b>), which were inactive against the sirtuin targets, presented anti-<i>T. cruzi</i> effects. In conclusion, our results showed the potential of <i>Anacardium occidentale</i> compounds for the development of potential sirtuin inhibitors and anti-<i>Trypanosoma cruzi</i> agents.https://www.mdpi.com/1420-3049/24/7/1299<i>Trypanosoma cruzi</i>sirtuins<i>Anacardium occidentale</i>drug discovery |
| spellingShingle | Tanira Matutino Bastos Helena Mannochio Russo Nilmar Silvio Moretti Sergio Schenkman Laurence Marcourt Mahabir Prashad Gupta Jean-Luc Wolfender Emerson Ferreira Queiroz Milena Botelho Pereira Soares Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins Molecules <i>Trypanosoma cruzi</i> sirtuins <i>Anacardium occidentale</i> drug discovery |
| title | Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins |
| title_full | Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins |
| title_fullStr | Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins |
| title_full_unstemmed | Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins |
| title_short | Chemical Constituents of <i>Anacardium occidentale</i> as Inhibitors of <i>Trypanosoma cruzi</i> Sirtuins |
| title_sort | chemical constituents of i anacardium occidentale i as inhibitors of i trypanosoma cruzi i sirtuins |
| topic | <i>Trypanosoma cruzi</i> sirtuins <i>Anacardium occidentale</i> drug discovery |
| url | https://www.mdpi.com/1420-3049/24/7/1299 |
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