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Molecules. 2019 Apr 3;24(7). pii: E1299. doi: 10.3390/molecules24071299.

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

Author information

1
Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, Brazil. tancomb@hotmail.com.
2
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. helenamrusso@gmail.com.
3
Departmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, Brazil. nilmar.moretti@unifesp.br.
4
Departmento de Microbiologia, Imunologia e Parasitologia, UNIFESP, São Paulo, SP 04039-032, Brazil. sergioschenkman@gmail.com.
5
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. laurence.marcourt@unige.ch.
6
Center for Pharmacognostic Research on Panamanian Flora (CIFLORPAN), College of Pharmacy, University of Panama, Panama 0824-00172, Panama. mahabirgupta@gmail.com.
7
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. jean-luc.wolfender@unige.ch.
8
School of Pharmaceutical Sciences, EPGL, University of Geneva, University of Lausanne, CMU, 1, Rue Michel Servet, 1211 Geneva, Switzerland. emerson.ferreira@unige.ch.
9
Instituto Gonçalo Moniz, FIOCRUZ, Salvador, BA 40296-710, Brazil. milena@bahia.fiocruz.br.

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.

KEYWORDS:

Anacardium occidentale; Trypanosoma cruzi; drug discovery; sirtuins

PMID:
30987092
PMCID:
PMC6479711
DOI:
10.3390/molecules24071299
[Indexed for MEDLINE]
Free PMC Article

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