taccalonolide AF | 1349904-81-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: taccalonolide AF
• 英文别名: [(1S,2S,3R,5S,7S,9S,10R,11R,12S,13S,14R,15R,16S,17S,18S,20S,23S,24S,25R,26R)-10,14,26-triacetyloxy-3,23-dihydroxy-11,15,17,23,24-pentamethyl-4,22-dioxo-8,19,21-trioxaoctacyclo[13.11.0.02,12.05,11.07,9.016,25.018,20.020,24]hexacosan-13-yl] acetate
• CAS: 1349904-81-9
• 化学式: C₃₆H₄₆O₁₅
• 分子量: 718.752
• InChiKey: HLIUEBSDHRWUNM-OYWXYWJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  51
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  214
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  箭根薯酮内酯A 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以100%的产率得到taccalonolide AF
  参考文献：
  名称：

  Potent Taccalonolides, AF and AJ, Inform Significant Structure–Activity Relationships and Tubulin as the Binding Site of These Microtubule Stabilizers

  摘要：

  The taccalonolides are a class of microtubule stabilizing agents isolated from plants of the genus Tacca. In efforts to define their structure activity relationships, we isolated five new taccalonolides, AC-AF and H2, from one fraction of an ethanol extract of Tacca plantaginea. The structures were elucidated using a combination of spectroscopic methods, including 1D and 2D NMR and HR-ESI-MS. Taccalonolide AJ, an epoxidation product of taccalonolide B, was generated by semisynthesis. Five of these taccalonolides demonstrated cellular microtubule-stabilizing activities and antiproliferative actions against cancer cells, with taccalonolide AJ exhibiting the highest potency with an IC50 value of 4.2 nM. The range of potencies of these compounds, from 4.2 nM to >50 mu M, for the first time provides the opportunity to identify specific structural moieties crucial for potent biological activities as well as those that impede optimal cellular effects. In mechanistic assays, taccalonolides AF and AJ stimulated the polymerization of purified tubulin, an activity that had not previously been observed for taccalonolides A and B, providing the first evidence that this class of microtubule stabilizers can interact directly with tubulin/microtubules. Taccalonolides AF and AJ were able to enhance tubulin polymerization to the same extent as paclitaxel but exhibited a distinct kinetic profile, suggesting a distinct binding mode or the possibility of a new binding site. The potencies of taccalonolides AF and AJ and their direct interaction with tubulin, together with the previous excellent in vivo antitumor activity of this class, reveal the potential of the taccalonolides as new anticancer agents.

  DOI：

  10.1021/ja209045k

文献信息

• [EN] NEW TACCALONOLIDE MICROTUBULE STABILIZERS<br/>[FR] NOUVEAUX STABILISATEURS TACCALONOLIDES DE MICROTUBULES
  申请人：UNIV TEXAS

  公开号：WO2012170573A3

  公开（公告）日：2013-06-13
• Potent Taccalonolides, AF and AJ, Inform Significant Structure–Activity Relationships and Tubulin as the Binding Site of These Microtubule Stabilizers
  作者：Jing Li、April L. Risinger、Jiangnan Peng、Zhongliang Chen、Lihong Hu、Susan L. Mooberry

  DOI：10.1021/ja209045k

  日期：2011.11.30

  The taccalonolides are a class of microtubule stabilizing agents isolated from plants of the genus Tacca. In efforts to define their structure activity relationships, we isolated five new taccalonolides, AC-AF and H2, from one fraction of an ethanol extract of Tacca plantaginea. The structures were elucidated using a combination of spectroscopic methods, including 1D and 2D NMR and HR-ESI-MS. Taccalonolide AJ, an epoxidation product of taccalonolide B, was generated by semisynthesis. Five of these taccalonolides demonstrated cellular microtubule-stabilizing activities and antiproliferative actions against cancer cells, with taccalonolide AJ exhibiting the highest potency with an IC50 value of 4.2 nM. The range of potencies of these compounds, from 4.2 nM to >50 mu M, for the first time provides the opportunity to identify specific structural moieties crucial for potent biological activities as well as those that impede optimal cellular effects. In mechanistic assays, taccalonolides AF and AJ stimulated the polymerization of purified tubulin, an activity that had not previously been observed for taccalonolides A and B, providing the first evidence that this class of microtubule stabilizers can interact directly with tubulin/microtubules. Taccalonolides AF and AJ were able to enhance tubulin polymerization to the same extent as paclitaxel but exhibited a distinct kinetic profile, suggesting a distinct binding mode or the possibility of a new binding site. The potencies of taccalonolides AF and AJ and their direct interaction with tubulin, together with the previous excellent in vivo antitumor activity of this class, reveal the potential of the taccalonolides as new anticancer agents.