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Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors

文献类型：期刊论文

作者Xu, Dandan2,5,6; Gong, Ying2,4; Zhang, Lianju2,5,6; Xiao, Fu1,2,3; Wang, Xinran1; Qin, Ji2,5,6; Tan, Lin2,5,6; Yang, Teng2,6; Lin, Zeng2,5,6; Xu, Zhongliang2,5
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2024-05-13
卷号67期号:10页码:8201-8224
ISSN号0022-2623
DOI10.1021/acs.jmedchem.4c00319
通讯作者Huang, Wei(huangwei@simm.ac.cn) ; Yang, Li(yangli@simm.ac.cn) ; Yang, Weibo(yweibo@simm.ac.cn)
英文摘要Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.
WOS关键词RECEPTOR-BINDING ; OSELTAMIVIR ; HEMAGGLUTININ ; FUSION ; RESISTANCE ; INSIGHTS ; OPTIMIZATION ; PERAMIVIR ; ZANAMIVIR ; THERAPY
资助项目National Natural Science Foundation of China ; Instrumentation and Service Center for Molecular Sciences at Westlake University[82373708] ; Instrumentation and Service Center for Molecular Sciences at Westlake University[22171275] ; Instrumentation and Service Center for Molecular Sciences at Westlake University[82325045] ; NSFC[23XD1424400] ; Shanghai Academic/Technology Research Leader[TD2020005] ; Hangzhou Innovation and Entrepreneurship Leading Team Project[2022M713265] ; China Postdoctoral Science Foundation
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001225298500001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/311297]  
专题新药研究国家重点实验室
通讯作者Huang, Wei; Yang, Li; Yang, Weibo
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Dandan,Gong, Ying,Zhang, Lianju,et al. Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024,67(10):8201-8224.
APA Xu, Dandan.,Gong, Ying.,Zhang, Lianju.,Xiao, Fu.,Wang, Xinran.,...&Yang, Weibo.(2024).Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,67(10),8201-8224.
MLA Xu, Dandan,et al."Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 67.10(2024):8201-8224.

入库方式： OAI收割

来源：上海药物研究所

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