title: 2,8-bis(trifluoromethyl)quinoline analogs show improved anti-Zika virus activity, compared to mefloquine.
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 EC50values 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.
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Giselle
authors.initials: G
authors.lastname: Barbosa-Lima
authors.affiliation: Instituto de Tecnologia em Fármacos - Far-Manguinhos, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Moraes
authors.affiliation: Instituto de Tecnologia em Fármacos - Far-Manguinhos, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Adriele da S
authors.initials: ADS
authors.lastname: Araújo
authors.affiliation: Instituto de Tecnologia em Fármacos - Far-Manguinhos, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Emerson T
authors.initials: ET
authors.lastname: da Silva
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: de Freitas
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Yasmine R
authors.initials: YR
authors.lastname: Vieira
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Marttorelli
authors.affiliation: Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: José Cerbino
authors.initials: JC
authors.lastname: Neto
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.affiliation: Instituto de Tecnologia em Fármacos - Far-Manguinhos, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Departamento de Química Orgânica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: marcos_souza@far.fiocruz.br.
authors.forename: Marcus V N
authors.initials: MVN
authors.lastname: de Souza
authors.affiliation: Instituto Oswaldo Cruz, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Centro de Desenvolvimento Tecnológico em Saúde, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; Instituto Nacional de Infectologia Evandro Chagas, Fiocruz - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Thiago Moreno L
authors.initials: TML
authors.lastname: Souza
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D015195:Drug Design; D015767:Mefloquine / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D000071244:Zika Virus / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D011804:Quinolines; D015767:Mefloquine
keywords: Antiviral; Mefloquine; Quinoline derivatives; Zika virus