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Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents

tetano

Editor, Senior Moderator
Bioorg Med Chem. 2019 Nov 9:115191. doi: 10.1016/j.bmc.2019.115191. [Epub ahead of print] [h=1]Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents.[/h]
Chintakrindi AS[SUP]1[/SUP], Gohil DJ[SUP]2[/SUP], Chowdhary AS[SUP]2[/SUP], Kanyalkar MA[SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Pharmaceutical Chemistry, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India. 2 Department of Virology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai 400012, India. 3 Department of Pharmaceutical Chemistry, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India. Electronic address: meenatul@gmail.com.

[h=3]Abstract[/h] We designed a series of substituted flavones and aurones as non-competitive H1N1 neuraminidase (NA) inhibitors and anti-influenza agents. The molecular docking studies showed that the designed flavones and aurones occupied 150-cavity and 430-cavity of H1N1-NA. We then synthesized these compounds and evaluated these for cytotoxicity, reduction in H1N1 virus yield, H1N1-NA inhibition and kinetics of inhibition. The virus yield reduction assay and H1N1-NA inhibition assay demonstrated that the compound 1f (4-methoxyflavone) had the lowest EC[SUB]50[/SUB] of 9.36 nM and IC[SUB]50[/SUB] of 8.74 μM respectively. Moreover, kinetic studies illustrated that compounds 1f and 2f had non-competitive inhibition mechanism.
Copyright ? 2019 Elsevier Ltd. All rights reserved.


[h=4]KEYWORDS:[/h] Aurones; Flavone; H1N1; Influenza; Neuraminidase; Non-competitive

PMID: 31744778 DOI: 10.1016/j.bmc.2019.115191
 
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