(E)-2-(benzylideneamino)-3′,6′-dihydroxyspiro[isoindoline-1,9′-xanthen]-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (E)-2-(benzylideneamino)-3′,6′-dihydroxyspiro[isoindoline-1,9′-xanthen]-3-one
• 化学式: C₂₇H₁₈N₂O₄
• 分子量: 434.451
• InChiKey: DVHMFGRQBCTDQC-LQKURTRISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.99
• 重原子数：
  33.0
• 可旋转键数：
  2.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  82.36
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  fluorescein free acid 在 硫酸 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 (E)-2-(benzylideneamino)-3′,6′-dihydroxyspiro[isoindoline-1,9′-xanthen]-3-one
  参考文献：
  名称：

  Fluorescein Hydrazones as Novel Nonintercalative Topoisomerase Catalytic Inhibitors with Low DNA Toxicity

  摘要：

  Fluorescein hydrazones (3a-3l) were synthesized in three steps with 86-91% overall yields. Topo I- and IIa-mediated relaxation and cell viability assay were evaluated. 3d inhibited 47% Topo I (camptothecin, 34%) and 20% Topo II (etoposide 24%) at 20 mu M. 3l inhibited 61% Topo II (etoposide 24%) at 20 mu M. 3d and 3l were further evaluated to determine their mode of action with diverse methods of kDNA decatenation, DNA-Topo cleavage complex, comet, DNA intercalating/unwinding, and Topo IIa-mediated ATP hydrolysis assays. 3d functioned as a nonintercalative dual inhibitor against the catalytic activities of Topo I and Topo II alpha. 3l acted as a Topo IIa specific nonintercalative catalytic inhibitor. 3d activated apoptotic proteins as it increased the level of cleaved capase-3 and cleaved PARP in a dose- and time-dependent manner. The dose- and time-dependent increase of G1 phase population was observed by treatment of 3d along with the increase of p27(kip1) and the decrease of cyclin D1 expression.

  DOI：

  10.1021/jm501263m

文献信息

• Fluorescein Hydrazones as Novel Nonintercalative Topoisomerase Catalytic Inhibitors with Low DNA Toxicity
  作者：A. F. M. Motiur Rahman、So-Eun Park、Adnan A. Kadi、Youngjoo Kwon

  DOI：10.1021/jm501263m

  日期：2014.11.13

  Fluorescein hydrazones (3a-3l) were synthesized in three steps with 86-91% overall yields. Topo I- and IIa-mediated relaxation and cell viability assay were evaluated. 3d inhibited 47% Topo I (camptothecin, 34%) and 20% Topo II (etoposide 24%) at 20 mu M. 3l inhibited 61% Topo II (etoposide 24%) at 20 mu M. 3d and 3l were further evaluated to determine their mode of action with diverse methods of kDNA decatenation, DNA-Topo cleavage complex, comet, DNA intercalating/unwinding, and Topo IIa-mediated ATP hydrolysis assays. 3d functioned as a nonintercalative dual inhibitor against the catalytic activities of Topo I and Topo II alpha. 3l acted as a Topo IIa specific nonintercalative catalytic inhibitor. 3d activated apoptotic proteins as it increased the level of cleaved capase-3 and cleaved PARP in a dose- and time-dependent manner. The dose- and time-dependent increase of G1 phase population was observed by treatment of 3d along with the increase of p27(kip1) and the decrease of cyclin D1 expression.