[:pb]Authors: Barbosa-Lima, G.; Moraes, A. M.; Araújo, A. S. ; Da Silva, E. T.; De Freitas, C. S.; Vieira, Y. R.; Marttorelli, A.; Neto, J. C.; Bozza, P. T.; De Souza, M. V.N. ; Souza, T. M. L.
Source: European Journal of Medicinal Chemistry, v. 127, p. 334-340, 2017
Publisher: Science Direct
Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC50 values of 0.8 μM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs.
Keywords: zika virus, quinoline derivatives, mefloquine, antiviral
Document Type: Research Article
Publication date: 15 de fevereiro de 2017