taccalonolide Z | 1330000-66-2

• 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 Z
• 英文别名: [(1S,2S,3R,5R,7S,9S,10R,11S,12S,13S,14R,15R,16S,17S,22S,23S,24R,25R)-10,13,14-triacetyloxy-3,5,22-trihydroxy-11,15,17,22,23-pentamethyl-4,21-dioxo-8,20-dioxaheptacyclo[13.10.0.02,12.05,11.07,9.016,24.019,23]pentacos-18-en-25-yl] acetate
• CAS: 1330000-66-2
• 化学式: C₃₆H₄₆O₁₅
• 分子量: 718.752
• InChiKey: FRPXJZJHOHOZJI-WVYQLPQSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  51
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  222
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  taccalonolide Z 在 二甲基二环氧乙烷 作用下， 以 二氯甲烷 为溶剂， 生成 taccalonolide Z epoxide
  参考文献：
  名称：

  Synthetic Reactions with Rare Taccalonolides Reveal the Value of C-22,23 Epoxidation for Microtubule Stabilizing Potency

  摘要：

  The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca. Taccalonolide AF is 231 times more potent than the major metabolite taccalonolide A and differs only by the oxidation of the C-22,23 double bond in A to an epoxy group in AF. In the current study, 10 other rare natural taccalonolides were epoxidized and in each case epoxidation improved potency. The epoxidation products of taccalonolide T and AI were the most potent, with IC50 values of 0.43 and 0.88 nM, respectively. These potent taccalonolides retained microtubule stabilizing effects, and T-epoxide demonstrated antitumor effects in a xenograft model of breast cancer. Additional reactions demonstrated that reduction of the C-6 ketone resulted in an inactive taccalonolide and that C-22,23 epoxidation restored its activity. These studies confirm the value of C-22,23 epoxidation as an effective strategy for increasing the potency of a wide range of structurally diverse taccalonolide microtubule stabilizers.

  DOI：

  10.1021/jm500619j

文献信息

• Identification and Biological Activities of New Taccalonolide Microtubule Stabilizers
  作者：Jiangnan Peng、April L. Risinger、Gary A. Fest、Evelyn M. Jackson、Gregory Helms、Lisa A. Polin、Susan L. Mooberry

  DOI：10.1021/jm200757g

  日期：2011.9.8

  The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods. The biological activities of the new taccalonolides, as well as taccalonolides A, B, E, N, R, and T, were evaluated. All nine taccalonolides display microtubule stabilizing activity, but profound differences in antiproliferative potencies were noted, with IC50 values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 mu M). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure-activity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.