Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates

	Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates
	Li, Haiwei 1; Li, Man 1; Xu, Renyang 1; Wang, Shouxin 3; Zhang, Yongmin 4; Zhang, Lihe 1; Zhou, Demin 1; Xiao, Sulong 1,2
	2019-02-01
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	163 页码:560-568
摘要	It is urgently necessary to develop more effective anti-influenza agents due to the continuous emergence of drug-resistant strains of influenza virus. Our earlier studies have identified that certain pentacyclic triterpene derivatives are effective inhibitors of influenza virus infection. In the present study, a series of C-28 modified pentacyclic triterpene derivatives via conjugation with a series of polyphenols were synthesized, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in MDCK (Madin-Darby canine kidney) cells were evaluated. Four compounds 23m, 23o, 23q and 23s displayed robust anti-influenza potency with averaged IC50 values at the low-micromole level, surpassing the potency of oseltamivir. In addition, the in vitro cytotoxic activity of the four conjugates against MDCK cells showed no toxicity at 100 mu M. Further mechanism studies of compound 23s, one of the best representative conjugates with IC50 value of 5.80 mu M and a selective index (SI) value of over 17.2, by hemagglutination inhibition (HI), surface plasmon resonance and molecular modeling indicated that this conjugate bound tightly to the viral envelope hemagglutinin (K-D = 15.6 mu M), thus blocking the invasion of influenza viruses into host cells. (C) 2018 Elsevier Masson SAS. All rights reserved.
关键词	Influenza virus Pentacyclic triterpene Polyphenol Entry inhibitor Hemagglutinin
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/64596
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Zhou, Demin; Xiao, Sulong
作者单位	1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 3.Jining Med Univ, Sch Pharm, Rizhao 276826, Peoples R China 4.Sorbonne Univ, Inst Parisien Chim Mol, CNRS UMR 8232, 4 Pl Jussieu, F-75005 Paris, France
推荐引用方式 GB/T 7714	Li, Haiwei,Li, Man,Xu, Renyang,et al. Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,163:560-568.
APA	Li, Haiwei.,Li, Man.,Xu, Renyang.,Wang, Shouxin.,Zhang, Yongmin.,...&Xiao, Sulong.(2019).Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,163,560-568.
MLA	Li, Haiwei,et al."Synthesis, structure activity relationship and in vitro anti-influenza virus activity of novel polyphenol-pentacyclic triterpene conjugates".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 163(2019):560-568.

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