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Chemical Constituents of Anacardium occidentale as Inhibitors of Trypanosoma cruzi Sirtuins.

  • Matutino Bastos T Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, Brazil. tancomb@hotmail.com.
  • Mannochio Russo H School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. helenamrusso@gmail.com.
  • Silvio Moretti N Departmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, Brazil. nilmar.moretti@unifesp.br.
  • Schenkman S Departmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, Brazil. sergioschenkman@gmail.com.
  • Marcourt L School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. laurence.marcourt@unige.ch.
  • Gupta MP Center for Pharmacognostic Research on Panamanian Flora (CIFLORPAN), College of Pharmacy, University of Panama, Panama 0824-00172, Panama. mahabirgupta@gmail.com.
  • Wolfender JL School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. jean-luc.wolfender@unige.ch.
  • Ferreira Queiroz E School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. emerson.ferreira@unige.ch.
  • Botelho Pereira Soares M Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, Brazil. milena@bahia.fiocruz.br.
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  • 2019-04-17
Published in:
  • Molecules (Basel, Switzerland). - 2019
Anacardium occidentale
Trypanosoma cruzi
drug discovery
sirtuins
Anacardium
Enzyme Activation
Enzyme Inhibitors
Molecular Structure
Parasitic Sensitivity Tests
Plant Extracts
Sirtuins
Trypanocidal Agents
Trypanosoma cruzi
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/194691
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