1, 2, 3-Triazolyl-4-oxoquinolines: A feasible beginning for promising chemical structures to inhibit oseltamivir-resistant influenza A and B viruses. Issue 24 (15th December 2015)

• Record Type: Journal Article
• 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.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 24(2015)
• Page Start: 7777
• Page End: 7784
• Publication Date: 2015-12-15
• Subjects: 1, 2, 3-Triazole -- 4-Oxoquinoline -- Influenza viruses -- Neuraminidase inhibitors -- Oseltamivir carboxylate -- Antiviral resistance; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.11.028
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical 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 derivative1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound1i inhibited influenza virus replication with an EC50 of 0.2 μM 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. 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 derivative1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound1i inhibited influenza virus replication with an EC50 of 0.2 μM 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.