taxchinin A | 146621-74-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: taxchinin A
• 英文别名: [(2S,4R,5R,5aS,6S,8S,9aR,10S,10aS)-5,6,10-triacetyloxy-2,8-dihydroxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-2,4,5,6,7,8,9a,10-octahydro-1H-benzo[g]azulen-4-yl] benzoate
• CAS: 146621-74-1
• 化学式: C₃₃H₄₂O₁₁
• 分子量: 614.69
• InChiKey: VETCXRGMQJYOHM-JGYXPHOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  taxchinin A 在 吡啶 、 咪唑 、 氢氟酸 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 [(2S,4R,5R,5aS,6S,9aS,10S,10aS)-5,6,10-triacetyloxy-2-hydroxy-10a-(2-hydroxypropan-2-yl)-3,5a-dimethyl-9-methylidene-8-oxo-1,2,4,5,6,7,9a,10-octahydrobenzo[g]azulen-4-yl] benzoate
  参考文献：
  名称：

  Dual-Functional abeo-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-κB Activation

  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.

  DOI：

  10.1021/jm400479p

文献信息

• Syntheses and cytotoxicities of the analogues of the taxoid brevifoliol
  作者：Sunil K. Chattopadhyay、Sarita Tripathi、Mahendra P. Darokar、Uzma Faridi、Brijesh Sisodia、Shubhra Negi、J. Kotesh Kumar、Suman P.S. Khanuja

  DOI：10.1016/j.ejmech.2007.09.002

  日期：2008.7

  Seven novel brevifoliol analogues have been synthesized by coupling brevifoliol and 2-monosubstituted-4-phenyl-1,3-oxazolidine carboxylic acid after removal of the protecting group with acid treatment. Brevifoliol and its synthesized analogues were tested for their cytotoxic activities against four different human cancer cell lines, oral (KB), breast (MCF-7), colon (CaCO2) and liver (HepG-2) as determined

  在用酸处理除去保护基团之后，通过将brevifoliol和2-单取代的-4-苯基-1,3-恶唑烷羧酸偶联，合成了七个新颖的brevifoliol类似物。如通过MTT测定所测定的，测试了短立叶醇及其合成的类似物对四种不同的人类癌细胞系，口服（KB），乳腺（MCF-7），结肠（CaCO2）和肝脏（HepG-2）的细胞毒性活性。C-13氧化的brevifoliol保留了显着的活性。在合成的七个类似物中，C-13氧化的brevifoliol-5- [N-叔丁氧基羰基氨基-（2'R，3'S）-3'-苯基异丝氨酸]类似物很有趣，因为它对肝癌表现出选择性和有效的细胞毒性细胞系为主。
• Synthesis, cytotoxic activity, and SAR analysis of the derivatives of taxchinin A and brevifoliol
  作者：Yu Zhao、Na Guo、Li-Guang Lou、Yu-Wen Cong、Li-Yan Peng、Qin-Shi Zhao

  DOI：10.1016/j.bmc.2008.03.041

  日期：2008.5

  Twenty-one derivatives of taxchinin A (1) and brevifoliol (2) were synthesized and evaluated for cytotoxicity against human non-small lung cancer (A549) cell line. Nine derivatives showed potent activity with IC(50) values from 0.48 to 6.22 mu M. 5-Oxo-13-TBDMS-taxchinin A (11) and5-oxo-13,15-epoxy-13-epi-taxchinin A (15) are the most potent derivatives, with IC(50) at 0.48 and 0.75 mu M, respectively. The structure - activity relationship (SAR) of these compounds established that exocyclic unsaturated ketone at ring C is the key structural element for the activity, while the alpha,beta-unsaturated ketone positioned at ring A has no effect for the activity. The significant cytotoxicity of derivatives 11 and 15 may be due to the conformational change in the taxane rings. The 3D-QSAR study was conducted on this series of compounds, which provided optimal predictive comparative molecular field (CoM-FA) model with cross-validated r(2) (q(2)) value of 0.64. (c) 2008 Elsevier Ltd. All rights reserved.
• Dual-Functional <i>abeo</i>-Taxane Derivatives Destabilizing Microtubule Equilibrium and Inhibiting NF-κB Activation
  作者：Yu Zhao、Jia Su、Masuo Goto、Susan L. Morris-Natschke、Yan Li、Qin-Shi Zhao、Zhu-Jun Yao、Kuo-Hsiung Lee

  DOI：10.1021/jm400479p

  日期：2013.6.13

  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.