(Z)-4-((R)-2,8-dimethyl-2-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)chroman-6-yloxy)-4-oxobut-2-enoic acid | 1258410-63-7

• 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: (Z)-4-((R)-2,8-dimethyl-2-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)chroman-6-yloxy)-4-oxobut-2-enoic acid
• 英文别名: (Z)-4-[[(2R)-2,8-dimethyl-2-[(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl]-3,4-dihydrochromen-6-yl]oxy]-4-oxobut-2-enoic acid
• CAS: 1258410-63-7
• 化学式: C₃₁H₄₂O₅
• 分子量: 494.671
• InChiKey: QWBBMKJEMHUHOY-RJEJERQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  马来酸酐 、 δ-生育三烯醇 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 反应 20.0h， 生成 (Z)-4-((R)-2,8-dimethyl-2-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)chroman-6-yloxy)-4-oxobut-2-enoic acid
  参考文献：
  名称：

  Redox-silent tocotrienol esters as breast cancer proliferation and migration inhibitors

  摘要：

  Tocotrienols are vitamin E members with potent antiproliferative activity against preneoplastic and neoplastic mammary epithelial cells with little or no effect on normal cell growth or functions. However, physicochemical and pharmacokinetic properties greatly limit their use as therapeutic agents. Tocotrienols' chemical instability, poor water solubility, NPC1L1-mediated transport, and rapid metabolism are examples of such obstacles which hinder the therapeutic use of these valuable natural products.Vitamin E esters like alpha-tocopheryl succinate were prepared to significantly improve chemical and metabolic stability, water solubility, and potency. Thus, 12 semisynthetic tocotrienol ester analogues 4-15 were prepared by direct esterification of natural tocotrienol isomers with various acid anhydrides or chlorides. Esters 4-15 were evaluated for their ability to inhibit the proliferation and migration of the mammary tumor cells +SA and MDA-MB-231, respectively. Esters 5, 9, and 11 effectively inhibited the proliferation of the highly metastatic +SA rodent mammary epithelial cells with IC50 values of 0.62, 0.51, and 0.86 mu M, respectively, at doses that had no effect on immortalized normal mouse CL-S1 mammary epithelial cells. Esters 4, 6, 8-10, and 13 inhibited 50% of the migration of the human metastatic MDA-MB-231 breast cancer cells at a single 5 mu M dose in wound-healing assay. The most active ester 9 was 1000-fold more water-soluble and chemically stable versus its parent a-tocotrienol (1). These findings strongly suggest that redox-silent tocotrienol esters may provide superior therapeutic forms of tocotrienols for the control of metastatic breast cancer. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.009

文献信息

• TOCOTRIENOL ESTERS
  申请人：El Sayed Khalid A.

  公开号：US20110196030A1

  公开（公告）日：2011-08-11

  Esters of tocotrienols having pharmacological activities pertinent to the treatment of breast cancer and other forms of cancer are disclosed herein. Among those compounds is (Z)-4-oxo-4-((R)-2,5,7,8-tetramethyl-2-((3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl)chroman-6-yloxy)but-2-enoic acid. Tocotrienol esters were used to inhibit the growth and migration of +SA mammary epithelial cells and highly metastatic human breast cancer MDA-MB-231 cells respectively.

  本文披露了对治疗乳腺癌和其他形式的癌症具有药理活性的生育三烯酚酯。其中包括（Z）-4-氧代-4-（（R）-2,5,7,8-四甲基-2-（（3E,7E）-4,8,12-三甲基十三碳烯-3,7,11-三烯基）色苷-6-氧基）丁-2-烯酸。生育三烯酚酯被用于抑制+SA乳腺上皮细胞和高度转移性的人乳腺癌MDA-MB-231细胞的生长和迁移。
• US8969303B2
  申请人：——

  公开号：US8969303B2

  公开（公告）日：2015-03-03
• Redox-silent tocotrienol esters as breast cancer proliferation and migration inhibitors
  作者：Fathy A. Behery、Ahmed Y. Elnagar、Mohamed R. Akl、Vikram B. Wali、Bilal Abuasal、Amal Kaddoumi、Paul W. Sylvester、Khalid A. El Sayed

  DOI：10.1016/j.bmc.2010.09.009

  日期：2010.11.15

  Tocotrienols are vitamin E members with potent antiproliferative activity against preneoplastic and neoplastic mammary epithelial cells with little or no effect on normal cell growth or functions. However, physicochemical and pharmacokinetic properties greatly limit their use as therapeutic agents. Tocotrienols' chemical instability, poor water solubility, NPC1L1-mediated transport, and rapid metabolism are examples of such obstacles which hinder the therapeutic use of these valuable natural products.Vitamin E esters like alpha-tocopheryl succinate were prepared to significantly improve chemical and metabolic stability, water solubility, and potency. Thus, 12 semisynthetic tocotrienol ester analogues 4-15 were prepared by direct esterification of natural tocotrienol isomers with various acid anhydrides or chlorides. Esters 4-15 were evaluated for their ability to inhibit the proliferation and migration of the mammary tumor cells +SA and MDA-MB-231, respectively. Esters 5, 9, and 11 effectively inhibited the proliferation of the highly metastatic +SA rodent mammary epithelial cells with IC50 values of 0.62, 0.51, and 0.86 mu M, respectively, at doses that had no effect on immortalized normal mouse CL-S1 mammary epithelial cells. Esters 4, 6, 8-10, and 13 inhibited 50% of the migration of the human metastatic MDA-MB-231 breast cancer cells at a single 5 mu M dose in wound-healing assay. The most active ester 9 was 1000-fold more water-soluble and chemically stable versus its parent a-tocotrienol (1). These findings strongly suggest that redox-silent tocotrienol esters may provide superior therapeutic forms of tocotrienols for the control of metastatic breast cancer. (C) 2010 Elsevier Ltd. All rights reserved.