1-(6,12-dihydroxy-2,2-dimethyl-3a,5,12,12a-tetrahydro-3bH-1,3,7,9-tetraoxa-4-azadicyclopenta[a,h]phenanthren-4-yl)-ethanone | 1111107-13-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 1-(6,12-dihydroxy-2,2-dimethyl-3a,5,12,12a-tetrahydro-3bH-1,3,7,9-tetraoxa-4-azadicyclopenta[a,h]phenanthren-4-yl)-ethanone
• 英文别名: 1-[(13R,14S,18R,19S)-9,19-dihydroxy-16,16-dimethyl-5,7,15,17-tetraoxa-12-azapentacyclo[11.7.0.02,10.04,8.014,18]icosa-1(20),2,4(8),9-tetraen-12-yl]ethanone
• CAS: 1111107-13-1
• 化学式: C₁₉H₂₁NO₇
• 分子量: 375.378
• InChiKey: VHVRCWNPKDABPJ-VYOUMLOHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  27
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  97.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(6,12-dihydroxy-2,2-dimethyl-3a,5,12,12a-tetrahydro-3bH-1,3,7,9-tetraoxa-4-azadicyclopenta[a,h]phenanthren-4-yl)-ethanone 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 1.0h， 以82%的产率得到1-(2,3,4,7-tetrahydroxy-2,4,4a,6-tetrahydro-3H-[1,3]dioxolo[4,5-j]phenanthridin-5-yl)-ethanone
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an Amaryllidaceae Isocarbostyril Derivative) as Potential Anticancer Agents

  摘要：

  Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (>= 1 mu M). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic 4, glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.

  DOI：

  10.1021/jm8013585
• 作为产物：
  描述：

  在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 68.0h， 以81%的产率得到1-(6,12-dihydroxy-2,2-dimethyl-3a,5,12,12a-tetrahydro-3bH-1,3,7,9-tetraoxa-4-azadicyclopenta[a,h]phenanthren-4-yl)-ethanone
  参考文献：
  名称：

  Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an Amaryllidaceae Isocarbostyril Derivative) as Potential Anticancer Agents

  摘要：

  Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (>= 1 mu M). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic 4, glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.

  DOI：

  10.1021/jm8013585

文献信息

• Structure−Activity Relationship Analysis of Novel Derivatives of Narciclasine (an <i>Amaryllidaceae</i> Isocarbostyril Derivative) as Potential Anticancer Agents
  作者：Laurent Ingrassia、Florence Lefranc、Janique Dewelle、Laurent Pottier、Véronique Mathieu、Sabine Spiegl-Kreinecker、Sébastien Sauvage、Mohamed El Yazidi、Mischaël Dehoux、Walter Berger、Eric Van Quaquebeke、Robert Kiss

  DOI：10.1021/jm8013585

  日期：2009.2.26

  Narciclasine (1) is a plant growth regulator that has been previously demonstrated to be proapoptotic to cancer cells at high concentrations (>= 1 mu M). Data generated in the present study show that narciclasine displays potent antitumor effects in apoptosis-resistant as well as in apoptosis-sensitive cancer cells by impairing the organization of the actin cytoskeleton in cancer cells at concentrations that are not cytotoxic (IC50 values of 30-90 nM). The current study further revealed that any chemical modification to the narciclasine backbone generally led to compounds of variable stability, weaker activity, or even the complete loss of antiproliferative effects in vitro. However, one hemisynthetic derivative of narciclasine, compound 7k, demonstrated by both the intravenous and oral routes higher in vivo antitumor activity in human orthotopic 4, glioma models in mice when compared to narciclasine at nontoxic doses. Narciclasine and compound 7k may therefore be of potential use to combat brain tumors.