Luciana Maria Ribeiro Antinarelli1,2, Raissa Soares Meinel3, Eduardo Antonio Ferraz Coelho1,4, Adilson David da Silva3, Elaine Soares Coimbra2. 1. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 2. Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil. 3. Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil. 4. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Abstract
OBJECTIVES: The in vitro antileishmanial effect of analogues of resveratrol (AR) present in the N-aryl imines and N-aryl hydrazones series was investigated. In addition, possible parasite targets were evaluated. METHODS: Antipromastigote activity of Leishmania amazonensis, L. braziliensis and L. infantum, as well as the cytotoxicity on macrophages was determined by MTT assay and L. braziliensis-infected macrophages effect by Giemsa stain. After staining, effects on the parasite targets were analysed by flow cytometry or by fluorescence microscopy. KEY- FINDINGS: Among the tested compounds, the derivative AR26 showed the best effect against promastigotes of all Leishmania species (IC50 < 3.0 µg/ml), being more active than miltefosine, the control drug. AR26 was also effective against amastigotes of L. braziliensis (IC50 = 15.9 µg/ml), with low toxicity to mammalian cells. The evaluation of mechanism of action of AR26 on L. braziliensis promastigotes indicates mitochondrial potential depolarization, plasma membrane permeabilization, interference in the progression of the cell cycle and accumulation of autophagic vacuoles. In addition, any increase of the reactive oxygen species levels was detected in the treated L. braziliensis-macrophages. CONCLUSIONS: Data indicate that the antileishmanial activity of AR26 is related to multitarget action, and the resveratrol analogues could be used in future studies as antileishmanial agent.
OBJECTIVES: The in vitro antileishmanial effect of analogues of resveratrol (AR) present in the N-aryl imines and N-aryl hydrazones series was investigated. In addition, possible parasite targets were evaluated. METHODS: Antipromastigote activity of Leishmania amazonensis, L. braziliensis and L. infantum, as well as the cytotoxicity on macrophages was determined by MTT assay and L. braziliensis-infected macrophages effect by Giemsa stain. After staining, effects on the parasite targets were analysed by flow cytometry or by fluorescence microscopy. KEY- FINDINGS: Among the tested compounds, the derivative AR26 showed the best effect against promastigotes of all Leishmania species (IC50 < 3.0 µg/ml), being more active than miltefosine, the control drug. AR26 was also effective against amastigotes of L. braziliensis (IC50 = 15.9 µg/ml), with low toxicity to mammalian cells. The evaluation of mechanism of action of AR26 on L. braziliensis promastigotes indicates mitochondrial potential depolarization, plasma membrane permeabilization, interference in the progression of the cell cycle and accumulation of autophagic vacuoles. In addition, any increase of the reactive oxygen species levels was detected in the treated L. braziliensis-macrophages. CONCLUSIONS: Data indicate that the antileishmanial activity of AR26 is related to multitarget action, and the resveratrol analogues could be used in future studies as antileishmanial agent.
Authors: Ayla das Chagas Almeida; Raíssa Soares Meinel; Yasmim Lopes Leal; Thiago P Silva; Nícolas Glanzmann; Débora Vasconcelos Costa Mendonça; Luísa Perin; Edézio Ferreira Cunha-Júnior; Eduardo A F Coelho; Rossana C N Melo; Adilson David da Silva; Elaine Soares Coimbra Journal: Parasitol Res Date: 2022-02-16 Impact factor: 2.289
Authors: Lais S Morais; Renata G Dusi; Daniel P Demarque; Raquel L Silva; Lorena C Albernaz; Sônia N Báo; Christian Merten; Luciana M R Antinarelli; Elaine S Coimbra; Laila S Espindola Journal: PLoS One Date: 2020-11-06 Impact factor: 3.240
Authors: Anutthaman Parthasarathy; Eli J Borrego; Michael A Savka; Renwick C J Dobson; André O Hudson Journal: J Biol Chem Date: 2021-02-18 Impact factor: 5.157