Discovery of new quinoline derivatives bearing 1-aryl-1,2,3-triazole motif as influenza H1N1 virus neuraminidase inhibitors

• Published in: Bioorganic chemistry Vol. 151; p. 107703
• Main Authors: Sabt, Ahmed, Khaleel, Eman F., Shaldam, Moataz A., Ebaid, Manal S., Mustafa Badi, Rehab, Allayeh, Abdou K., Eldehna, Wagdy M., Dziadek, Jaroslaw
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2024
• Subjects: 1-Aryl-1,2,3-triazole; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Hydrazineylquinoline; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - enzymology; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Molecular Structure; Neuraminidase - antagonists & inhibitors; Neuraminidase - metabolism; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Structure-Activity Relationship; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Molecular dynamics; Antiviral agents; Hydrazineylquinoline; 1-Aryl-1,2,3-triazole; Molecular docking
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107703

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•Sixteen quinoline-triazole hybrids 6a-h and 9a-h were prepared as H1N1 antiviral compounds.•6d, 6e, and 9b showed promising H1N1 antiviral activity with SI values of 15.8, 37, and 29.15.•4e showed significant antiviral activity during the replication mechanism with 82.2% inhibition activity.•4d displayed the best Neuraminidase inhibitory activity with IC50 = 0.3019 ± 0.014 µg/ml.•A docking study was conducted for 6d, 6e, 9b to justify their efficacy as neuraminidase inhibitors.•Molecular dynamic simulations and binding free energy calculations were conducted for 6d.
Sporadically and periodically, influenza outbreaks threaten global health and the economy. Antigen drift-induced influenza virus mutations hamper antiviral drug development. Thus, a novel antiviral agent is urgently needed to address medication inefficacy issues. Herein, sixteen new quinoline-triazole hybrids 6a-h and 9a-h were prepared and evaluated in vitro against the H1N1 virus. In particular, 6d, 6e, and 9b showed promising H1N1 antiviral activity with selective index (SI) CC50/IC50 values of 15.8, 37, and 29.15. After that, the inhibition rates for various mechanisms of action (virus replication, adsorption, and virucidal activity) were investigated for the most efficient candidates 6d, 6e, and 9b. Additionally, their ability to inhibit neuraminidase was evaluated. With an IC50 value of 0.30 µM, hybrid 6d demonstrated effective and comparable inhibitory activity to Oseltamivir. Ultimately, molecular modeling investigations, encompassing molecular docking and molecular dynamic simulations, were conducted to provide a scientific basis for the observed antiviral results.