2,3,4-trihydroxy-7-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one | 1019642-64-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 英文名称: 2,3,4-trihydroxy-7-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one
• 英文别名: (2S,3R,4S,4aR)-2,3,4-trihydroxy-7-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}-3,4,4a,5-tetrahydro[1,3]dioxolo[4,5-j]phenanthridine-6(2H)-one；(2S,3R,4S,4aR)-2,3,4-trihydroxy-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one
• CAS: 1019642-64-8
• 化学式: C₂₀H₂₃NO₁₂
• 分子量: 469.402
• InChiKey: RUUNRUPODCEPNR-RIVBPKAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  208
• 氢给体数：
  8
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  acetic acid 2,3-diacetoxy-7-O-(2',3',4',6'-tetra-O-benzoyl-β-D-glucopyranosyl)-6-oxo-2,3,4,4a,5,6-hexahydro[1,3]dioxolo[4,5-j]phenanthridin-4-yl ester 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 17.0h， 以94%的产率得到2,3,4-trihydroxy-7-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-3,4,4a,5-tetrahydro-2H-[1,3]dioxolo[4,5-j]phenanthridin-6-one
  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

• ISOCARBOSTYRIL ALKALOID DERIVATIVES HAVING ANTI-PROLIFERATIVE AND ANTI-MIGRATORY ACTIVITIES
  申请人：Ingrassia Laurent

  公开号：US20100076005A1

  公开（公告）日：2010-03-25

  Isocarbostyril alkaloid derivatives having an anti-proliferative and anti-migratory activities are disclosed. In particular, compounds of formula (I) or (II), as well as stereoisomers, tautomers, racemates, prodrugs, metabolites thereof, pharmaceutically acceptable salt and/or solvate are encompassed which are useful in the treatment and prophylaxis of cancer. Methods of preparation are also disclosed.

  揭示了具有抗增殖和抗迁移活性的异喹啉生物碱衍生物。具体来说，公开了符合以下化学式(I)或(II)的化合物，以及其立体异构体、互变异构体、消旋体、前药、代谢物、药学上可接受的盐和/或溶剂，这些化合物在癌症的治疗和预防中很有用。还公开了制备方法。
• 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.