Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors

doi:10.1016/j.bmcl.2009.10.006

	Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors
	Zhang, Quan 1; Jiang, Zhi-Yong 1; Luo, Jie 1; Ma, Yun-Bao 1; Liu, Ji-Feng 1; Guo, Rui-Hua 1; Zhang, Xue-Mei1 ; Zhou, Jun1 ; Niu, Wei 2; Du, Fei-Fei 2; Li, Li 2; Li, Chuan 2; Chen, Ji-Jun1
	2009-12-01
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN	0960-894X
卷号	19 期号:23 页码:6659-6665
摘要	Thirty-two tetra-acylated derivatives of alisol A were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. Among the series of alisol A derivatives examined, five analogues were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells. These results also provide interesting structure-activity relationships of tetra-acylalisol A derivatives. Compounds tetra-acetyl alisol A (A1), tetra-methoxyacetyl alisol A (A23), and tetra-ethoxyacetyl alisol A (A24) exhibited high activities against secretion of HBsAg with IC(50) values of 0.0048, 0.0044, and 0.014 mM, respectively, HBeAg with IC(50) values of 0.011, 0.012, and 0.018 mM, respectively, and remarkable selective index values SI(HBsAg) > 333, SI(HBeAg) > 145; SI(HBsAg) = 209, SI(HBeAg) = 77; and SI(HBsAg) > 200, SI(HBeAg) > 156, respectively. Additional studies in rats showed that compound A1 has favorable pharmacokinetic prosperities for further development purpose, with elimination half-time (t(1/2)) of 1.63 h and oral bioavailability (F) of 40.9%. (C) 2009 Elsevier Ltd. All rights reserved.
关键词	Anti-hbv Activity Protostane-type Triterpene Alisol a Derivatives Chemical Modification
学科领域	Chemistry, Medicinal ; Chemistry, Organic
DOI	10.1016/j.bmcl.2009.10.006
收录类别	SCI
语种	英语
WOS记录号	WOS:000271430400036
引用统计	被引频次：20[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/4138
专题	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 W China, Kunming Inst Bot, Kunming 650204, Peoples R China 2.Chinese Acad Sci, Shanghai Ctr DMPK Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Quan,Jiang, Zhi-Yong,Luo, Jie,et al. Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2009,19(23):6659-6665.
APA	Zhang, Quan.,Jiang, Zhi-Yong.,Luo, Jie.,Ma, Yun-Bao.,Liu, Ji-Feng.,...&Chen, Ji-Jun.(2009).Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,19(23),6659-6665.
MLA	Zhang, Quan,et al."Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 19.23(2009):6659-6665.

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