methyl (1S,3R,7R,8S,13R,15S)-15-hydroxy-3,7-dimethyl-14-methylidenetetracyclo[11.2.1.02,11.03,8]hexadec-2(11)-ene-7-carboxylate | 1221154-77-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (1S,3R,7R,8S,13R,15S)-15-hydroxy-3,7-dimethyl-14-methylidenetetracyclo[11.2.1.02,11.03,8]hexadec-2(11)-ene-7-carboxylate
• CAS: 1221154-77-3
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.467
• InChiKey: ZQSIJACVJWFGDD-QSWGWULZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl grandiflorenate 在 selenium(IV) oxide 、 水 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 17.0h， 以53%的产率得到15α-hydroxy-9(11)-dehydro-ent-Kaurensaeuremethylester
  参考文献：
  名称：

  Synthesis and induction of apoptosis signaling pathway of ent-kaurane derivatives

  摘要：

  Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15 alpha-acetoxykaurenoic acid (26) and 16 alpha-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 mu M of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.064

文献信息

• Synthesis and induction of apoptosis signaling pathway of ent-kaurane derivatives
  作者：Idaira Hueso-Falcón、Natalia Girón、Pilar Velasco、Juan M. Amaro-Luis、Angel G. Ravelo、Beatriz de las Heras、Sonsoles Hortelano、Ana Estevez-Braun

  DOI：10.1016/j.bmc.2009.11.064

  日期：2010.2

  Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15 alpha-acetoxykaurenoic acid (26) and 16 alpha-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 mu M of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells. (C) 2009 Elsevier Ltd. All rights reserved.