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

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	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
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2019-02-01
卷号	163 页码:560-568
关键词	Influenza virus Pentacyclic triterpene Polyphenol Entry inhibitor Hemagglutinin
ISSN号	0223-5234
英文摘要	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.
资助项目	National Natural Science Foundation of China[81573269] ; National Natural Science Foundation of China[21572015] ; National Natural Science Foundation of China[81530090] ; National Natural Science Foundation of China[21877007] ; National Natural Science Foundation of China[21702007]
语种	英语
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/64595]
专题	昆明植物研究所_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.