tetano
Editor, Senior Moderator
Chem Biodivers. 2018 Dec 9. doi: 10.1002/cbdv.201800577. [Epub ahead of print]
[h=1]Synthesis and biological evaluation of substituted indole and its analogs as influenza A virus inhibitors.[/h] Zhang X[SUP]1[/SUP], Zhang GN[SUP]2[/SUP], Wang Y[SUP]2[/SUP], Zhu M[SUP]2[/SUP], Wang J[SUP]2[/SUP], Li Z[SUP]3[/SUP], Li D[SUP]1[/SUP], Cen S[SUP]2[/SUP], Wang Y[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1, D3, D9, G1, G3, G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06-5.77 μM) and low cytotoxicity (CC50 values up to and beyond 100 μM). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.
[h=4]KEYWORDS:[/h] Influenza A virus *substitution and bioisosteric replacement * indole* naphthol * coumarin
PMID: 30536577 DOI: 10.1002/cbdv.201800577
[h=1]Synthesis and biological evaluation of substituted indole and its analogs as influenza A virus inhibitors.[/h] Zhang X[SUP]1[/SUP], Zhang GN[SUP]2[/SUP], Wang Y[SUP]2[/SUP], Zhu M[SUP]2[/SUP], Wang J[SUP]2[/SUP], Li Z[SUP]3[/SUP], Li D[SUP]1[/SUP], Cen S[SUP]2[/SUP], Wang Y[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1, D3, D9, G1, G3, G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06-5.77 μM) and low cytotoxicity (CC50 values up to and beyond 100 μM). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.
[h=4]KEYWORDS:[/h] Influenza A virus *substitution and bioisosteric replacement * indole* naphthol * coumarin
PMID: 30536577 DOI: 10.1002/cbdv.201800577