Screening and identification of 3-aryl-quinolin-2-one derivatives as antiviral agents against influenza A |
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| Authors: | Huimin Cheng Liangbing Fu Xia Yang Yujian Yang Zhening Zhang Yuan Tao Junting Wan Zhengchao Tu Jianxin Chen Yingjun Li |
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| Institution: | 1. XtalPi Inc. (Shenzhen Jingtai Technology Co., Ltd), Shenzhen, China;2. School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, China;3. Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China;4. Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China;5. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China;6. International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, China |
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| Abstract: | Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure–activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 μM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents. |
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| Keywords: | antiviral agents copper iodide catalysis H1N1 H3N2 influenza virus quinolinone |
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