Author | Bastos, Tanira Matutino | |
Author | Russo, Helena Mannochio | |
Author | Moretti, Nilmar Silvio | |
Author | Schenkman, Sergio | |
Author | Marcourt, Laurence | |
Author | Gupta, Mahabir Prashad | |
Author | Wolfender, Jean-Luc | |
Author | Queiroz, Emerson Ferreira | |
Author | Soares, Milena Botelho Pereira | |
Access date | 2019-08-06T17:59:50Z | |
Available date | 2019-08-06T17:59:50Z | |
Document date | 2019 | |
Citation | BASTOS,Tanira Matutino et al. Chemical Constituents of Anacardium occidentale as Inhibitors of Trypanosoma cruzi Sirtuins. Molecules, v. 24, p. 1-13, 2019. | pt_BR |
ISSN | 1420-3049 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/34633 | |
Sponsorship | Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant 015/22031-0 to S.S. and N.M., Grant 2018/09948-0 to N.M.); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). SS and M.S are the recipients of a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). | pt_BR |
Language | eng | pt_BR |
Publisher | MDPI | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Sirtuins | pt_BR |
Subject in Portuguese | Anacardium occidentale | pt_BR |
Subject in Portuguese | Descoberta de drogas | pt_BR |
Title | Chemical Constituents of Anacardium occidentale as Inhibitors of Trypanosoma cruzi Sirtuins | pt_BR |
Type | Article | pt_BR |
DOI | 10.3390/molecules24071299 | |
Abstract | 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 (Anacardium occidentale, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (1, 2), cardanol (3, 4), and anacardic acid (5, 6) were investigated. The two anacardic acids (5, 6) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (2) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (2), with an EC50 value of 12.25 µM, similar to that of benznidazole. Additionally, compounds (1, 4), which were inactive against the sirtuin targets, presented anti-T. cruzi effects. In conclusion, our results showed the potential of Anacardium occidentale compounds for the development of potential sirtuin inhibitors and anti-Trypanosoma cruzi agents. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. Geneva, Switzerland. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departmento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal de São Paulo. Departmento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. Geneva, Switzerland. | pt_BR |
Affilliation | University of Panama. College of Pharmacy. Center for Pharmacognostic Research on Panamanian Flora. Panama, Panama. | pt_BR |
Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. Geneva, Switzerland. | pt_BR |
Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. Geneva, Switzerland. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Sirtuins | pt_BR |
Subject | Anacardium occidentale | pt_BR |
Subject | Drug discovery | pt_BR |