Anti-HBV agents. Part 3: Preliminary structure-activity relationships of tetra-acylalisol A derivatives as potent hepatitis B virus inhibitors
Zhang, Quan1; Jiang, Zhi-Yong1; Luo, Jie1; Ma, Yun-Bao1; Liu, Ji-Feng1; Guo, Rui-Hua1; Zhang, Xue-Mei1; Zhou, Jun1; Niu, Wei2; Du, Fei-Fei2; Li, Li2; Li, Chuan2; Chen, Ji-Jun1
2009-12-01
发表期刊BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN0960-894X
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
资助信息National Natural Science Foundation of China (NSFC) [30672522]; New Drug Development, Ministry of Science and Technology [2009ZX09103- 108]; Chinese Academy of Sciences [GJHZ200818]; CAS- Croucher Foundation [CAS- CF07/08. SC03]
学科领域Chemistry, Medicinal ; Chemistry, Organic
DOI10.1016/j.bmcl.2009.10.006
收录类别SCI
语种英语
WOS研究方向Pharmacology & Pharmacy ; Chemistry
WOS类目Chemistry, Medicinal ; Chemistry, Organic
WOS记录号WOS:000271430400036
引用统计
被引频次:16[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
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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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