2. Academic Validation
  3. 1,2,3-Triazolyl-4-oxoquinolines: A feasible beginning for promising chemical structures to inhibit oseltamivir-resistant influenza A and B viruses

1,2,3-Triazolyl-4-oxoquinolines: A feasible beginning for promising chemical structures to inhibit oseltamivir-resistant influenza A and B viruses

  • Bioorg Med Chem. 2015 Dec 15;23(24):7777-84. doi: 10.1016/j.bmc.2015.11.028.
Fernanda da C S Boechat 1,  Carolina Q Sacramento 2,  Anna C Cunha 1,  Fernanda S Sagrillo 1,  Christiane M Nogueira 1,  Natalia Fintelman-Rodrigues 2,  Osvaldo Santos-Filho 3,  Cecília S Riscado 1,  Luana da S M Forezi 1,  Letícia V Faro 1,  Leonardo Brozeguini 1,  Isakelly P Marques 1,  Vitor F Ferreira 1,  Thiago Moreno L Souza 2,  Maria Cecília B V de Souza 4
Affiliations

Affiliations

  • 1 Universidade Federal Fluminense, Instituto de Química-Outeiro de São João Batista, s/n°.Campus do Valonguinho, Centro, Niterói, RJ CEP 24020-150, Brazil.
  • 2 Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Vírus Respiratórios, NIC-WHO, Rio de Janeiro, RJ CEP 21041-360, Brazil; Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Imunofarmacologia, Rio de Janeiro, RJ CEP 21041-360, Brazil; Fundação Oswaldo Cruz, Centro de Desenvolvimento Tecnológico em Saúde, Rio de Janeiro, RJ CEP 21041-360, Brazil.
  • 3 Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Vírus Respiratórios, NIC-WHO, Rio de Janeiro, RJ CEP 21041-360, Brazil.
  • 4 Universidade Federal Fluminense, Instituto de Química-Outeiro de São João Batista, s/n°.Campus do Valonguinho, Centro, Niterói, RJ CEP 24020-150, Brazil. Electronic address: mceciliabvs@gmail.com.
PMID: 26643220 DOI: 10.1016/j.bmc.2015.11.028
Abstract

We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound 1i inhibited Influenza Virus replication with an EC50 of 0.2μM with less cytotoxicity than OST, and also inhibited different OST-resistant NAs. These results suggest that 1,2,3-triazolyl-4-oxoquinolines represent promising lead molecules for further anti-influenza drug design.

Keywords

1,2,3-Triazole; 4-Oxoquinoline; Antiviral resistance; Influenza viruses; Neuraminidase inhibitors; Oseltamivir carboxylate.

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