Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17955
Title: N-(2-(arylmethylimino)ethyl)-7-chloroquinolin-4-amine derivatives, synthesized by thermal and ultrasonic means, are endowed with anti-Zika virus activity
Authors: Lima, Giselle Barbosa
Pinto, Ligia S. da Silveira
Kaiser, Carlos R.
Wardell, James L.
Freitas, Caroline S. de
Vieira, Yasmine R.
Marttorelli, Andressa
Cerbino Neto, José
Bozza, Patrícia T.
Wardell, Solange M. S. V.
Souza, Marcus V. N. de
Souza, Thiago M. L.
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / University of Aberdeen. Department of Chemistry. Aberdeen, Scotland, UK.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil
CHEMSOL. Aberdeen, Scotland, UK.
Universidade Federal do Rio de Janeiro. Departamento de Química Orgânica. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Abstract: Zika virus (ZIKV), an emerging Flavivirus, was recently associated with severe neurological complications and congenital diseases. Therefore, development of antiviral agents capable of inhibiting ZIKV replication is urgent. Chloroquine is a molecule with a confirmed safety history for use with pregnant women, and has been found to exhibit anti-ZIKV activity at concentrations around 10 μM. This suggests that modifications to the chloroquine structure could be promising for obtaining more effective anti-ZIKV agents. Here, we report the ability of a series of N-(2-(arylmethylimino)ethyl)-7-chloroquinolin-4-amine derivatives to inhibit ZIKV replication in vitro. We have found that the quinoline derivative, N-(2-((5-nitrofuran-2-yl)methylimino)ethyl)-7-chloroquinolin-4-amine, 40, was the most potent compound within this series, reducing ZIKV replication by 72% at 10 μM. Compound 40 exhibits an EC50 value of 0.8 ± 0.07 μM, compared to that of chloroquine of 12 ± 3.2 μM. Good activities were also obtained for other compounds, including those with aryl groups = phenyl, 4-fluorophenyl, 4-nitrophenyl, 2,6-dimethoxyphenyl, 3-pyridinyl and 5-nitrothien-2-yl. Syntheses of these quinoline derivatives have been obtained both by thermal and ultrasonic means. The ultrasonic method produced comparable yields to the thermal (reflux) method in very much shorter times 30-180 s compared to 30-180 min reactions times. These results indicate that this group of compounds is a good follow-up point for the potential discovery of new drugs against the Zika disease.
Keywords: Zika Virus
Quinoline derivatives
Sonochemical method
keywords: Zika Virus
Derivados de quinolina
Método sonoquímico
Issue Date: 2017
Publisher: Elsevier
Citation: LIMA, Giselle Barbosa; et al. N-(2-(arylmethylimino)ethyl)-7-chloroquinolin-4-amine derivatives, synthesized by thermal and ultrasonic means, are endowed with anti- Zika virus activity. European Journal of Medicinal Chemistry, v.127, p. 434-441, 2017.
DOI: 10.1016/j.ejmech.2017.01.007
ISSN: 0223-5234
Copyright: open access
Appears in Collections:INI - Artigos de Periódicos
CDTS - Artigos de Periódicos
Farmanguinhos - Artigos de Periódicos
IOC - Artigos de Periódicos

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