| Author | Coimbra, Elaine Soares | |
| Author | Antinarelli, Luciana Maria Ribeiro | |
| Author | Silva, Natalia P. | |
| Author | Souza, Isabela de Oliveira | |
| Author | Meinel, Raissa Soares | |
| Author | Rocha, Marcele Neves | |
| Author | Soares, Rodrigo Pedro Pinto | |
| Author | Silva, Adilson D. da | |
| Access date | 2017-02-09T17:34:25Z | |
| Available date | 2017-02-09T17:34:25Z | |
| Document date | 2016 | |
| Citation | COIMBRA, Elaine Soares et al. Quinoline derivatives: Synthesis, leishmanicidal activity and involvement of mitochondrial xidative stress as mechanism of action. Chem Biol Interact. 2016, v. 260, p. 50-57, 2012. | pt_BR |
| ISSN | 0009-2797 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/17778 | |
| Language | eng | pt_BR |
| Publisher | Elsevier Ltd | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | Leishmania | pt_BR |
| Subject in Portuguese | Quinolines | pt_BR |
| Title | Quinoline derivatives: Synthesis, leishmanicidal activity and involvement of mitochondrial xidative stress as mechanism of action | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.cbi.2016.10.017. | |
| Abstract | Leishmaniasis comprise a spectrum of diseases caused by protozoa parasites from the genus Leishmania, affecting millions of people worldwide, mainly in subtropical countries. Most antileishmanial drugs are highly toxic, present resistance issues or require long-term treatment. Consequently, new drugs are urgently needed. Quinoline-containing compounds have displayed an impressive array of biological properties over the years, including antileishmanial activity. In the present study, we report the synthesis and evaluation of novel quinoline derivatives (QuinDer) against Leishmania species and cytotoxic effect on mammalian cells. The ROS production and mitochondrial membrane potential analyses were also studied. The compound QuinDer1 showed activity on L. amazonensis and L. braziliensis promastigotes and this compound exhibited a strong inhibition of the proliferation of L. amazonensis amastigotes at nM concentration (IC50 of 0.0911 μM), being 139 times more active than miltefosine (IC50 of 12.7 μM), used as reference drug. This compound presents low cytotoxicity toward murine macrophages and human erythrocytes. In addition, promastigotes of L. amazonensis treated with the compound QuinDer1 present high generation of ROS levels with low alterations in mitochondrial membrane potential and maintenance of parasite membrane integrity. No substantial NO production in infected-macrophages treated with this compound was detected. These results suggest that the compound QuinDer 1 is a potent and selective antileishmanial agent by mitochondrial oxidative | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Parasitologia, Microbiologia e Imunologia. Juiz de Fora, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Parasitologia, Microbiologia e Imunologia. Juiz de Fora, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Parasitologia, Microbiologia e Imunologia. Juiz de Fora, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brazil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Fundaçao Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil | pt_BR |
| Affilliation | Universidade Federal Juiz de Fora. Instituto de Ciências Exatas. Departamento de Química. Juiz de Fora, MG, Brazil | pt_BR |
| Subject | Chemotherapy | pt_BR |
| Subject | Mitochondrial membrane potential | pt_BR |
| Subject | Oxidative stress | pt_BR |
| Subject | Quinolines | pt_BR |
| Subject | ROS production | pt_BR |
| Embargo date | 2035-01-01 | |
