1,6,6-trimethyl-11-(2-(trifluoromethyl)phenyl)-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1,6,6-trimethyl-11-(2-(trifluoromethyl)phenyl)-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole
• 英文别名: 5,17,17-Trimethyl-9-[2-(trifluoromethyl)phenyl]-3-oxa-8,10-diazapentacyclo[10.8.0.02,6.07,11.013,18]icosa-1(12),2(6),4,7(11),9,13(18),19-heptaene；5,17,17-trimethyl-9-[2-(trifluoromethyl)phenyl]-3-oxa-8,10-diazapentacyclo[10.8.0.02,6.07,11.013,18]icosa-1(12),2(6),4,7(11),9,13(18),19-heptaene
• 化学式: C₂₇H₂₃F₃N₂O
• 分子量: 448.488
• InChiKey: WYVRMLFMQFDTBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  33
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  邻三氟甲基苯甲醛 、 丹参酮 IIA 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 生成 1,6,6-trimethyl-11-(2-(trifluoromethyl)phenyl)-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole
  参考文献：
  名称：

  Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo

  摘要：

  Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogues TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated. All compounds, particularly TA12, markedly inhibited the proliferation, migration, and invasion of MDA-MB-231cells. TA12 also prominently blocked cancer cell metastasis in blood vessels and surrounding tissues in zebrafish xenograft model. Further studies showed that the mechanisms may involve S-phase arrest pathway, which was probably caused by inducing reactive oxygen species production and activating DNA damage. These results indicated that the Tan-IIA-based analogues of imidazole derivates can act as potent antimetastasis agents.

  DOI：

  10.1021/acs.jmedchem.8b01018

文献信息

• Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo
  作者：Qiong Wu、Kangdi Zheng、Xiaoting Huang、Li Li、Wenjie Mei

  DOI：10.1021/acs.jmedchem.8b01018

  日期：2018.12.13

  Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogues TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated. All compounds, particularly TA12, markedly inhibited the proliferation, migration, and invasion of MDA-MB-231cells. TA12 also prominently blocked cancer cell metastasis in blood vessels and surrounding tissues in zebrafish xenograft model. Further studies showed that the mechanisms may involve S-phase arrest pathway, which was probably caused by inducing reactive oxygen species production and activating DNA damage. These results indicated that the Tan-IIA-based analogues of imidazole derivates can act as potent antimetastasis agents.