Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

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 relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents
	Chen, Hao 1,2; Ma, Yun-Bao 1; Huang, Xiao-Yan 1; Geng, Chang-An1 ; Zhao, Yong 1,2; Wang, Li-Jun 1; Guo, Rui-Hua 1; Liang, Wen-Juan 1,2; Zhang, Xue-Mei1 ; Chen, Ji-Jun1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2014-05-15
卷号	24 期号:10 页码:2353-2359
关键词	Anti-HBV activity Dehydroandrographolide and andrographolide derivatives Structure-activity relationships Octanol-water partition coefficients
ISSN号	0960-894X
通讯作者	Chen,JJ (reprint author),Chinese Acad Sci,State Key Lab Phytochem & Plant Resources West C,Kunming Inst Bot,Kunming 650201,Peoples R China. ; chenjj@mail.kib.ac.cn
英文摘要	Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 mu M and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal logP value of 1.78 and logD values. Structureactivity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs. (C) 2014 Elsevier Ltd. All rights reserved.
学科主题	Pharmacology & Pharmacy ; Chemistry
类目[WOS]	Chemistry, Medicinal ; Chemistry, Organic
研究领域[WOS]	Pharmacology & Pharmacy ; Chemistry
关键词[WOS]	PARTITION-COEFFICIENTS ; DRUG DISCOVERY ; IN-VITRO ; INHIBITORS ; CONSTITUENTS ; ANALOGS ; DESIGN ; VIVO
收录类别	SCI ; IC
资助信息	National Natural Science Foundation of China for Distinguished Young Scholars [81025023]; National Natural Science Foundation of China [81202436]; West Light Foundation of the Chinese Academy of Sciences; Youth Innovation Promotion Association, CAS
语种	英语
WOS记录号	WOS:000335517300024
公开日期	2014-06-23
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/18112]
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
作者单位	1.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West C, Kunming Inst Bot, Kunming 650201, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Chen, Hao,Ma, Yun-Bao,Huang, Xiao-Yan,et al. Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2014,24(10):2353-2359.
APA	Chen, Hao.,Ma, Yun-Bao.,Huang, Xiao-Yan.,Geng, Chang-An.,Zhao, Yong.,...&Chen, Ji-Jun.(2014).Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,24(10),2353-2359.
MLA	Chen, Hao,et al."Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 24.10(2014):2353-2359.