9,10-[1,3]-dioxinocamptothecin

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 9,10-[1,3]-dioxinocamptothecin
• 英文别名: (18S)-18-ethyl-18-hydroxy-6,8,20-trioxa-13,24-diazahexacyclo[12.11.0.03,12.04,9.015,24.017,22]pentacosa-1,3(12),4(9),10,13,15,17(22)-heptaene-19,23-dione
• 化学式: C₂₂H₁₈N₂O₆
• 分子量: 406.395
• InChiKey: UIEOLZNSHMCWCW-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  98.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 10-羟基喜树碱 在 三氟甲磺酸 作用下， 以 neat (no solvent) 为溶剂， 反应 12.0h， 生成 9,10-[1,3]-dioxinocamptothecin
  参考文献：
  名称：

  A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability

  摘要：

  Oral administration of camptothecin (CPT) derivatives and other antitumoral agents is being actively developed in order to improve the quality of life of patients with cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar apoptosis cell mechanism and high ability to inhibit DNA synthesis in HeLa, Caco-2, A375 and MDA-MB-231 cell lines. Furthermore, in vitro and in situ pharmacokinetics transport values obtained for CDiox displayed more favorable absorption profile than CPT and Topotecan.

  DOI：

  10.1016/j.ejmech.2014.06.050