(3aS,9R,9aS,9bS)-9-methoxy-6,9-dimethyl-3-methylidene-4,5,7,8,9a,9b-hexahydro-3aH-azuleno[4,5-b]furan-2-one | 1403357-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (3aS,9R,9aS,9bS)-9-methoxy-6,9-dimethyl-3-methylidene-4,5,7,8,9a,9b-hexahydro-3aH-azuleno[4,5-b]furan-2-one
• CAS: 1403357-78-7
• 化学式: C₁₆H₂₂O₃
• 分子量: 262.349
• InChiKey: KBFSPVPOZNQSBP-RZLSGREXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 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：

  parthenolide 在 三氟化硼乙醚 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 10.25h， 生成 (3aS,9R,9aS,9bS)-9-methoxy-6,9-dimethyl-3-methylidene-4,5,7,8,9a,9b-hexahydro-3aH-azuleno[4,5-b]furan-2-one
  参考文献：
  名称：

  Guaianolide Sesquiterpene Lactones, a Source To Discover Agents That Selectively Inhibit Acute Myelogenous Leukemia Stem and Progenitor Cells

  摘要：

  Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34(+)CD38(-)) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches.

  DOI：

  10.1021/jm301064b

文献信息

• Synthesis of Micheliolide Derivatives and Their Activities against AML Progenitor Cells
  作者：Wei-Wei Ma、Qian-Qian Shi、Ya-Hui Ding、Jing Long、Quan Zhang、Yue Chen

  DOI：10.3390/molecules18055980

  日期：——

  Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant cell line HL-60/A. As to multi-drug resistant AML progenitor cells KG-1a, MCL and some of its derivatives maintained significant activities, and only 1.1–2.7 fold activity reductions were observed when compared with the activities against HL-60, while doxorubicin showed 20-fold activity reduction. Our study demonstrated that the C4 hydroxyl group of MCL might not only be a suitable position for structural modifications, but also be a starting point for the design of appropriate molecular probes to explore the specific targets in the progenitor cell line KG-1a.

  合成了在C4位点的羟基经过醚化或酯化的Micheliolide（MCL）衍生物，并评估其对不同急性髓性白血病（AML）细胞系的活性。这些衍生物对AML细胞系HL-60及多柔比星耐药细胞系HL-60/A表现出了相当的活性。至于多药耐药AML祖细胞KG-1a，MCL及其某些衍生物维持了显著的活性，与对HL-60的活性相比，仅观察到1.1-2.7倍的活性减少，而多柔比星则显示出20倍的活性减少。我们的研究表明，MCL的C4羟基不仅是结构修饰的合适位置，也是设计合适分子探针以探索KG-1a祖细胞系中特定靶标的起点。
• Guaianolide Sesquiterpene Lactones, a Source To Discover Agents That Selectively Inhibit Acute Myelogenous Leukemia Stem and Progenitor Cells
  作者：Quan Zhang、Yaxin Lu、Yahui Ding、Jiadai Zhai、Qing Ji、Weiwei Ma、Ming Yang、Hongxia Fan、Jing Long、Zhongsheng Tong、Yehui Shi、Yongsheng Jia、Bin Han、Wenpeng Zhang、Chuanjiang Qiu、Xiaoyan Ma、Qiuying Li、Qianqian Shi、Haoliang Zhang、Dongmei Li、Jing Zhang、Jianping Lin、Lu-Yuan Li、Yingdai Gao、Yue Chen

  DOI：10.1021/jm301064b

  日期：2012.10.25

  Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34(+)CD38(-)) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches.