| Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-kappa B Activation | |
Zhao, Yu1,2; Su, Jia1,3; Goto, Masuo2; Morris-Natschke, Susan L.2; Li, Yan1 ; Zhao, Qin-Shi1; Yao, Zhu-Jun4; Lee, Kuo-Hsiung2,5,6
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| 通讯作者 | Zhao, QS (reprint author), Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650204, Peoples R China. ; qinshizhao@mail.kib.ac.cn ; yaoz@mail.sioc.ac.cn ; khlee@unc.edu |
| 2013-06-13 | |
| 发表期刊 | JOURNAL OF MEDICINAL CHEMISTRY
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| ISSN | 0022-2623 |
| 卷号 | 56期号:11页码:4749-4757 |
| 摘要 | Taxchinin A, with a 11(15 -> 1)-abeo-taxane skeleton, is a major, but inactive taxoid contained in leaves of Taxus chinensis. In our design of dual-functional antitumor abeo-taxane derivatives, two fragments from antitumor agents with different molecular targets (the N-acyl-3'-phenylisoserine side chain from the antimitotic agent paclitaxel and an alpha,beta-unsaturated carbonyl system from NF-kappa B inhibitors) were incorporated into the scaffold of taxchinin A. The resulting compounds displayed broad inhibitory effects against proliferation of tumor cell lines, with notable selectivity toward colon cancer, melanoma, and renal cancer, when evaluated in the NCI-60 human tumor cell line screening panel. On the basis of the NCI-60 assay data, structure-activity relationship (SAR) correlations were elucidated. Mechanistic studies indicated that this new compound type can both destabilize microtubules and inhibit NF-kappa B activation, thereby inducing tumor cell apoptosis. This first report of the dual-functional taxoid-core compounds thus provides new opportunities for future drug development based on natural axoid scaffolds. |
| 关键词 | Natural-products Biological-activity Cancer-therapy Paclitaxel Taxol Resistance Drugs Chemotherapy Parthenolide Brevifoliol |
| 学科领域 | Chemistry, Medicinal |
| 收录类别 | SCI ; IC |
| 语种 | 英语 |
| WOS记录号 | WOS:000320640900042 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/16763 |
| 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 West Ch, Kunming Inst Bot, Kunming 650204, Peoples R China 2.Univ N Carolina, Nat Prod Res Labs, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA 3.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, EISU Chem Biol Div, Shanghai 200032, Peoples R China 5.Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA 6.China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung 40447, Taiwan |
| 推荐引用方式 GB/T 7714 | Zhao, Yu,Su, Jia,Goto, Masuo,et al. Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-kappa B Activation[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(11):4749-4757. |
| APA | Zhao, Yu.,Su, Jia.,Goto, Masuo.,Morris-Natschke, Susan L..,Li, Yan.,...&Lee, Kuo-Hsiung.(2013).Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-kappa B Activation.JOURNAL OF MEDICINAL CHEMISTRY,56(11),4749-4757. |
| MLA | Zhao, Yu,et al."Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-kappa B Activation".JOURNAL OF MEDICINAL CHEMISTRY 56.11(2013):4749-4757. |
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