High selective antileishmanial activity of vanadium complex with stilbene derivative.
Leishmaniasis is a group of disease caused by different species of the parasite Leishmania affecting millions of people worldwide. Conventional therapy relies on multiple parenteral injections with pentavalent antimonials which exhibit high toxicity and various side effects have been reported. Hence, the research for an effective and low toxic effect drug is necessary. In the present work, the synthesis, spectroscopic and analytical characterizations of stilbene derivative (H2Salophen) and its vanadium complex (VOSalophen) are reported. Besides the chemical ancillary information, investigation of the leishmanicidal effects of these compounds were provided. The biological assays against promastigote and amastigote forms of L. amazonensis have been shown that VOSalophen exhibited a strong antiparasitic activity (IC50 of 6.65 and 3.51 μM, respectively). Furthermore, the leishmanicidal activity was concentration and time-dependent. Regarding toxicity and selectivity on mammalian cells, VOSalophen have not caused significant damage to human erythrocytes in all concentrations tested and VOSalophen was almost seven times more destructive for the intracellular parasite than for macrophages. Furthermore, the leishmanicidal activity of VOSalophen in promastigote forms of L. amazonensis could be associated to mitochondrial dysfunction and increase of the reactive oxygen species (ROS) production. In L. amazonensis-infected macrophages, VOSalophen induces ROS production and a microbicidal action NO-dependent. Our biological results indicate the effective and selective action of VOSalophen against L. amazonensis and the leishmanicidal effect can be associated to parasite disorders and immumodulatory effects.
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil.
Patrícia de Almeida
Pde A
Machado
LQBin - Laboratório de Química BioInorgânica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil.
Vinícius Zamprogno
VZ
Mota
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil.
Ana Clara de Lima
AC
Cavalli
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, 36036-900 Juiz de Fora, MG, Brazil.
Gustavo Senra Gonçalves
GS
de Carvalho
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, 36036-900 Juiz de Fora, MG, Brazil.
Adilson David
AD
Da Silva
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil.
Jacy
J
Gameiro
LQBin - Laboratório de Química BioInorgânica, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil.
Alexandre
A
Cuin
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, 33036-900 Juiz de Fora, MG, Brazil. Electronic address: elaine.coimbra@ufjf.edu.br.
Elaine Soares
ES
Coimbra
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species; D012459:Salicylates / Q000494:pharmacology*; D017968:Vanadium Compounds / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D017382:Reactive Oxygen Species; D012459:Salicylates; D017968:Vanadium Compounds; C090416:salophen
Leishmania amazonensis; Mitochondrial dysfunction; Nitric oxide; Stilbenes; Vanadium complex