Authors: Pinheiro, Alessandra C.; Kaiser, Carlos R.; Lourenço, Maria C.S.; de Souza, Marcus V.N.; Wardell, Solange M.S.V.; Wardell, James L. Lima, G.B.; Moraes, A.M.; Araújo, A.S.; Da Silva, E.T.; De Freitas, C.S.; Vieira, Y.R.; Marttorelli, A.; Cerbino Neto, J.; Bozza, P.T.; De Souza, M.V.N.; Souza, T.M.L.
Source: European Journal of Medicinal Chemistry, Volume 127, p. 334-340, 2017.
Publisher: Elsevier
Abstract
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 DOI: 10.1016/j.ejmech.2016.12.058 Publication date: 15 de Fevereiro de 2017 [:en]
Authors: Pinheiro, Alessandra C.; Kaiser, Carlos R.; Lourenço, Maria C.S.; de Souza, Marcus V.N.; Wardell, Solange M.S.V.; Wardell, James L. Lima, G.B.; Moraes, A.M.; Araújo, A.S.; Da Silva, E.T.; De Freitas, C.S.; Vieira, Y.R.; Marttorelli, A.; Cerbino Neto, J.; Bozza, P.T.; De Souza, M.V.N.; Souza, T.M.L.
Source: European Journal of Medicinal Chemistry, Volume 127, p. 334-340, 2017.
Publisher: Elsevier
Abstract
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 DOI: 10.1016/j.ejmech.2016.12.058 Publication date: 15 de Fevereiro de 2017 [:]
