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

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 24; pp. 7777 - 7784
• Main Authors: Boechat, Fernanda da C.S., Sacramento, Carolina Q., Cunha, Anna C., Sagrillo, Fernanda S., Nogueira, Christiane M., Fintelman-Rodrigues, Natalia, Santos-Filho, Osvaldo, Riscado, Cecília S., Forezi, Luana da S.M., Faro, Letícia V., Brozeguini, Leonardo, Marques, Isakelly P., Ferreira, Vitor F., Souza, Thiago Moreno L., de Souza, Maria Cecília B.V.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-12-2015
• Subjects: 1,2,3-Triazole; 4-Oxoquinoline; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral resistance; Drug Design; Drug Resistance, Viral; Humans; Influenza A virus - drug effects; Influenza A virus - enzymology; Influenza B virus - drug effects; Influenza B virus - enzymology; Influenza viruses; Influenza, Human - drug therapy; Influenza, Human - virology; Molecular Docking Simulation; Neuraminidase - antagonists & inhibitors; Neuraminidase - metabolism; Neuraminidase inhibitors; Oseltamivir - pharmacology; Oseltamivir carboxylate; Quinolones - chemistry; Quinolones - pharmacology; Triazoles - chemistry; Triazoles - pharmacology; Influenza viruses; Oseltamivir carboxylate; 1,2,3-Triazole; Neuraminidase inhibitors; Antiviral resistance; 4-Oxoquinoline
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2015.11.028

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. [Display omitted]
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.