Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors.
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.
['Zhang|Xuandi|X|http://orcid.org/0000-0001-8544-8442', 'Zhang|Guo-Ning|GN|', 'Wang|Yujia|Y|', 'Zhu|Mei|M|', 'Wang|Juxian|J|', 'Li|Ziqiang|Z|', 'Li|Donghui|D|', 'Cen|Shan|S|', 'Wang|Yucheng|Y|']
D000998:Antiviral Agents D015195:Drug Design D006801:Humans D007211:Indoles D009980:Influenza A virus D013329:Structure-Activity Relationship
indole influenza A virus cytotoxicity substitution and bioisosteric replacement antiviral activity coumarin naphthol