(R)-10-(oxiran-2-ylmethyl)acridin-9(10H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (R)-10-(oxiran-2-ylmethyl)acridin-9(10H)-one
• 英文别名: 10-[[(2R)-oxiran-2-yl]methyl]acridin-9-one
• 化学式: C₁₆H₁₃NO₂
• 分子量: 251.285
• InChiKey: KRMZERAQRFRQKQ-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-10-(oxiran-2-ylmethyl)acridin-9(10H)-one 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (R,Z)-10-(3-(3-((1-(3-chlorophenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene)methyl)-1H-indol-1-yl)-2-hydroxypropyl)acridin-9(10H)-one
  参考文献：
  名称：

  Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase

  摘要：

  Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI(50) 0.3 mu M. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI(50) in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.

  DOI：

  10.1016/j.bmcl.2019.126631
• 作为产物：
  描述：

  右旋环氧氯丙烷 、 吖啶酮 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以55%的产率得到(R)-10-(oxiran-2-ylmethyl)acridin-9(10H)-one
  参考文献：
  名称：

  Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase

  摘要：

  Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI(50) 0.3 mu M. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI(50) in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.

  DOI：

  10.1016/j.bmcl.2019.126631

文献信息

• Structural tuning of acridones for developing anticancer agents targeting dihydrofolate reductase
  作者：Harpreet Singh、Manpreet Kaur、Harpreet Kaur、Indu Sharma、Anmol Bhandari、Gurcharan Kaur、Palwinder Singh

  DOI：10.1016/j.bmcl.2019.126631

  日期：2019.10

  Targeting dihydrofolate reductase, here, we report the tumor growth inhibitory activity of substituted acridones. The screening of the molecules over 60 cell line panel of human cancer cells identified (S)-oxiran-2-ylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate (19) with average GI(50) 0.3 mu M. The specificity of the compound to CCRF-CEM, MOLT-4 and SR cell lines of leukemia and SW-620, SF268, LOXIMVI, ACHN and MCF7 cancerous cells exhibiting GI(50) in the nM range was observed. C6 Glioma cells treated with compound 19 showed differentiated cell morphology and cell cycle arrest in G2/M phase. The interactions of the compound with dihydrofolate reductase were ascertained with the help of enzyme immunoassays, molecular docking and molecular dynamic studies.