3-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one | 1338059-07-6

• 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: 3-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one
• 英文别名: 3-farnesyloxycoumarin；3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienoxy]chromen-2-one
• CAS: 1338059-07-6
• 化学式: C₂₄H₃₀O₃
• 分子量: 366.5
• InChiKey: KFEFEJGESATHEF-NKFKFSAASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-羟基香豆素 、 反,反-法呢基溴 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.42h， 生成 3-(((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)oxy)-2H-chromen-2-one
  参考文献：
  名称：

  Pancreatic anticancer activity of a novel geranylgeranylated coumarin derivative

  摘要：

  A series of hydroxycoumarin derivatives has been synthesized and evaluated against human pancreatic PANC-1 cancer cells under nutrient-deprived conditions. Several compounds exhibited 100% preferential cytotoxicity at low micromolar concentrations under nutrition starvation, and showed no cytotoxicity under nutrient-rich conditions. In this study, a novel geranylgeranylated ether coumarin derivative 9 was found to exhibit the highest cytotoxic activity of 6.25 mu M within 24 h. The preferential anti-tumor activity exhibited by compound 9 against PANC-1 under low oxygen and nutrient environment illustrates its great potential as a promising lead structure for the development of novel agents to combat pancreatic cancer. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.005

文献信息

• Pancreatic anticancer activity of a novel geranylgeranylated coumarin derivative
  作者：Tehsina Devji、Claire Reddy、Christina Woo、Suresh Awale、Shigetoshi Kadota、Dora Carrico-Moniz

  DOI：10.1016/j.bmcl.2011.08.005

  日期：2011.10

  A series of hydroxycoumarin derivatives has been synthesized and evaluated against human pancreatic PANC-1 cancer cells under nutrient-deprived conditions. Several compounds exhibited 100% preferential cytotoxicity at low micromolar concentrations under nutrition starvation, and showed no cytotoxicity under nutrient-rich conditions. In this study, a novel geranylgeranylated ether coumarin derivative 9 was found to exhibit the highest cytotoxic activity of 6.25 mu M within 24 h. The preferential anti-tumor activity exhibited by compound 9 against PANC-1 under low oxygen and nutrient environment illustrates its great potential as a promising lead structure for the development of novel agents to combat pancreatic cancer. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and SAR studies of mono O-prenylated coumarins as potent 15-lipoxygenase inhibitors
  作者：Mehrdad Iranshahi、Atena Jabbari、Ala Orafaie、Robabeh Mehri、Soudabeh Zeraatkar、Taraneh Ahmadi、Maliheh Alimardani、Hamid Sadeghian

  DOI：10.1016/j.ejmech.2012.09.006

  日期：2012.11

  All of the mono isopentenyloxy, -geranyloxy and -farnesyloxy derivatives of coumarin were synthesized and their inhibitory potency against soybean 15-lipoxygenase (SLO) and human 15-lipoxygenase-1 (HLO-1) were determined. Amongst the synthetic analogs, 5-farnesyloxycoumarin showed the most potent inhibitory activity against SLO (IC50 = 0.8 mu M) while 6-farnesyloxycoumarin was the strongest HLO-1 inhibitor (IC50 = 1.3 mu M). The IC50 variations of the farnesyl derivatives for HLO-1 (1.3 to similar to 75 mu M) were much higher than that observed for SLO (0.8-5.8 mu M). SAR studies showed that hydrogen bonding, CH/pi, anion-pi and S-O=C interactions with Fe-III-OH, Leu408, Glu357 and Met419 were the distinct intermolecular interactions which can lead to important role of the coumarin substitution site in HLO-1 inhibitory potency, respectively. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of isoprenylated coumarins as potential anti-pancreatic cancer agents
  作者：Maria Jun、Alyssa F. Bacay、James Moyer、Andrew Webb、Dora Carrico-Moniz

  DOI：10.1016/j.bmcl.2014.08.038

  日期：2014.10

  A series of isoprenylated coumarins has been designed, synthesized, and evaluated against human pancreatic adenocarcinoma cell line PANC-1 under nutrient-rich and nutrient-deprived conditions. The compounds described investigate the effect of isoprenyl chain length and positioning on cell growth inhibition. The majority of these compounds displayed cytotoxicity against PANC-1 cells selectively in the absence of essential amino acids, glucose, and serum, and showed no cytotoxicity under nutrient-rich conditions. In this study, compound 6 exhibited the highest cytotoxic activity with an LC50 value of 4μM and induced apoptosis-like morphological changes in PANC-1 cells after a 24-h incubation. The evaluated structure-activity relationships show that substitution at the 6-position and the presence of a farnesyl isoprenyl tail are important structural features for enhanced preferential cytotoxicity. These findings provide important information to designing other structural analogues for potential application as novel pancreatic antitumor agents.