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
Source PublicationBIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN0960-894X
Volume19Issue:23Pages:6659-6665
AbstractThirty-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.
KeywordAnti-hbv Activity Protostane-type Triterpene Alisol a Derivatives Chemical Modification
Subject AreaChemistry, Medicinal ; Chemistry, Organic
DOI10.1016/j.bmcl.2009.10.006
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Chemistry
WOS SubjectChemistry, Medicinal ; Chemistry, Organic
WOS IDWOS:000271430400036
Citation statistics
Cited Times:17[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/4138
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.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
Recommended Citation
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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