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Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential

Published online by Cambridge University Press:  13 February 2019

Layzon Antonio Lemos da Silva ,
Milene Höehr de Moraes ,
Marcus Tullius Scotti ,
Luciana Scotti ,
Rafaela de Jesus Souza ,
Judith L. Nantchouang Ouete ,
Maique Weber Biavatti ,
Mario Steindel  and
Louis Pergaud Sandjo Open the ORCID record for Louis Pergaud Sandjo [Opens in a new window]
Layzon Antonio Lemos da Silva
Affiliation:
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil
Milene Höehr de Moraes
Affiliation:
Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis-SC, Brazil
Marcus Tullius Scotti
Affiliation:
Post-Graduate Program in Natural and Synthetic Bioactive Products Federal University of Paraíba Cidade Universitária-Castelo Branco III, João Pessoa, PB, Brazil
Luciana Scotti
Affiliation:
Post-Graduate Program in Natural and Synthetic Bioactive Products Federal University of Paraíba Cidade Universitária-Castelo Branco III, João Pessoa, PB, Brazil
Rafaela de Jesus Souza
Affiliation:
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil
Judith L. Nantchouang Ouete
Affiliation:
Department of Organic Chemistry, University of Yaoundé I, P. O. Box 812, Yaoundé, Cameroon
Maique Weber Biavatti
Affiliation:
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil
Mario Steindel
Affiliation:
Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, 88040-900, Florianópolis-SC, Brazil
Louis Pergaud Sandjo*
Affiliation:
Department of Pharmaceutical Sciences, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil
*
Author for correspondence: Louis Pergaud Sandjo, E-mail: [email protected]
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Abstract

The study aims to evaluate the antiprotozoal activities of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Compounds 1–20 were obtained and identified by using chromatographic and spectroscopic techniques. The antiparasitic assays were performed on the intracellular form of T. cruzi and L. amazonensis using human leukaemic THP-1 cells as the host. The mechanism of action of the most active compounds was explored in silico by molecular docking using T. cruzi trypanothione reductase (TR) as a target, whereas the in vitro studies were performed by enzymatic assay using T. cruzi recombinant TR. In addition, the mitochondrial membrane potential was evaluated by flow cytometry. Two flavonoids, one triterpene and three acetogenins showed from high to moderate trypanocidal activities with IC50 values ranging 3.6–37.2 µm while three of the metabolites were moderately leishmanicidal. The molecular docking study revealed interactions between TR and the most trypanocidal compounds 1 (abyssinone IV) and 2 (atalantoflavone). In contrast, both showed no effect on TR in vitro. For the mitochondrial membrane potential assay, atalantoflavone (2) displayed a dose-dependent depolarization. On the basis of the aforementioned results, this compound's structure could be chemically explored in order to develop more potent trypanocidal derivatives.

Keywords

Antiparasitic evaluationLeishmania amazonensismitochondrial membrane potentialprenylated flavonesTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 146 , Issue 7 , June 2019 , pp. 849 - 856
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Copyright
Copyright © Cambridge University Press 2019 

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