tetano
Editor, Senior Moderator
Bioorg Chem
. 2024 Aug 6:151:107703.
doi: 10.1016/j.bioorg.2024.107703. Online ahead of print. Discovery of new quinoline derivatives bearing 1-aryl-1,2,3-triazole motif as influenza H1N1 virus neuraminidase inhibitors
Ahmed Sabt[SUP] 1 [/SUP], Eman F Khaleel[SUP] 2 [/SUP], Moataz A Shaldam[SUP] 3 [/SUP], Manal S Ebaid[SUP] 4 [/SUP], Rehab Mustafa Badi[SUP] 2 [/SUP], Abdou K Allayeh[SUP] 5 [/SUP], Wagdy M Eldehna[SUP] 6 [/SUP], Jaroslaw Dziadek[SUP] 7 [/SUP]
Affiliations
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) CC[SUB]50[/SUB]/IC[SUB]50[/SUB] 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 IC[SUB]50[/SUB] 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.
Keywords: 1-Aryl-1,2,3-triazole; Antiviral agents; Hydrazineylquinoline; Molecular docking; Molecular dynamics.
. 2024 Aug 6:151:107703.
doi: 10.1016/j.bioorg.2024.107703. Online ahead of print. Discovery of new quinoline derivatives bearing 1-aryl-1,2,3-triazole motif as influenza H1N1 virus neuraminidase inhibitors
Ahmed Sabt[SUP] 1 [/SUP], Eman F Khaleel[SUP] 2 [/SUP], Moataz A Shaldam[SUP] 3 [/SUP], Manal S Ebaid[SUP] 4 [/SUP], Rehab Mustafa Badi[SUP] 2 [/SUP], Abdou K Allayeh[SUP] 5 [/SUP], Wagdy M Eldehna[SUP] 6 [/SUP], Jaroslaw Dziadek[SUP] 7 [/SUP]
Affiliations
- PMID: 39137601
- DOI: 10.1016/j.bioorg.2024.107703
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) CC[SUB]50[/SUB]/IC[SUB]50[/SUB] 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 IC[SUB]50[/SUB] 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.
Keywords: 1-Aryl-1,2,3-triazole; Antiviral agents; Hydrazineylquinoline; Molecular docking; Molecular dynamics.