Synthesis and structure-activity relationship study of arylsulfonamides as novel potent H5N1 inhibitors

Eur J Med Chem. 2018 Nov 5:159:206-216. doi: 10.1016/j.ejmech.2018.09.065.

Yongshi Yu ¹, Qi Tang ², Zhichao Xu ¹, Siliang Li ², Mengyu Jin ¹, Zixuan Zhao ², Chune Dong ¹, Shuwen Wu ³, Hai-Bing Zhou ⁴

Affiliations

1 State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China.
2 State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China.
3 State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China. Electronic address: shuwenwu@hotmail.com.
4 State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address: zhouhb@whu.edu.cn.

PMID: 30292897 DOI: 10.1016/j.ejmech.2018.09.065

Abstract

H5N1 virus, one subtype of highly pathogenic influenza A virus in human Infection, has recently received attention due to its unpredictable and high mortality. In this study, a series of arylsulfonamide derivatives were identified as improved H5N1 inhibitors for the influenza treatment by systematic structure-activity relationship investigation. Among them, the most potent H5N1 inhibitor 3h exhibited excellent Antiviral activity against H5N1 virus with EC₅₀ value of 0.006 μM and selectivity index 33543.3. Moreover, the molecular docking of 3h with M2 proton channel protein provides practical way for understanding the inhibition of H5N1 with this kind of compounds.

Keywords

Arylsulfonamide inhibitors; H5N1 virus; High mortality; Structure-activity relationship.

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