1-(3,4,5-trimethoxy)phenyl-3-hydroxymethyl-9-methyl-β-carboline | 1145668-26-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-(3,4,5-trimethoxy)phenyl-3-hydroxymethyl-9-methyl-β-carboline
• 英文别名: [9-Methyl-1-(3,4,5-trimethoxyphenyl)pyrido[3,4-b]indol-3-yl]methanol
• CAS: 1145668-26-3
• 化学式: C₂₂H₂₂N₂O₄
• 分子量: 378.428
• InChiKey: BKZGDAKZHLKOTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  65.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3,4,5-trimethoxy)phenyl-3-hydroxymethyl-9-methyl-β-carboline 在 manganese(IV) oxide 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以74%的产率得到1-(3,4,5-trimethoxy)phenyl-9-methyl-β-carboline-3-carboxaldehyde
  参考文献：
  名称：

  Synthesis and biological evaluation of piperazine group-linked bivalent β-carbolines as potential antitumor agents

  摘要：

  一系列具有3-亚甲基单元之间的哌嗪基间隔的二价β-咔啉类化合物被合成，并评估了它们的体外细胞毒活性。化合物7e和7g表现出强大的细胞毒活性。

  DOI：

  10.1039/c5md00312a
• 作为产物：
  描述：

  ethyl 1-(3,4,5-trimethoxy)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylate 在 锂硼氢 、 sodium hydride 、 sulfur 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 1-(3,4,5-trimethoxy)phenyl-3-hydroxymethyl-9-methyl-β-carboline
  参考文献：
  名称：

  Synthesis and biological evaluation of piperazine group-linked bivalent β-carbolines as potential antitumor agents

  摘要：

  一系列具有3-亚甲基单元之间的哌嗪基间隔的二价β-咔啉类化合物被合成，并评估了它们的体外细胞毒活性。化合物7e和7g表现出强大的细胞毒活性。

  DOI：

  10.1039/c5md00312a

文献信息

• Design and synthesis of dithiocarbamate linked β-carboline derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability
  作者：Ahmed Kamal、Manda Sathish、V. Lakshma Nayak、Vunnam Srinivasulu、Botla Kavitha、Yellaiah Tangella、Dinesh Thummuri、Chandrakant Bagul、Nagula Shankaraiah、Narayana Nagesh

  DOI：10.1016/j.bmc.2015.07.037

  日期：2015.9

  Further, the induction of apoptosis by these derivatives was confirmed by Annexin V-FITC and Hoechst staining assays. However, both biophysical as well as molecular docking studies suggested a combilexin-type of interaction between these derivatives and DNA, unlike simple β-carbolines. With a view to understand their mechanism of action, DNA topoisomerase II (topo II) inhibition assay was also performed.

  设计并合成了一系列新的分别在-1、3和9位带有苯基，二硫代氨基甲酸酯和H /甲基取代基的β-咔啉-二硫代氨基甲酸酯衍生物。已评估了这些衍生物8a – l和13a – l及其起始前体（7a – d和12a – d）对某些人类癌细胞系的体外细胞毒性活性。在测试的衍生物中，7c，12c，8a，8d，8i，8j，8k，8l和13d – 1对大多数测试癌细胞系表现出相当大的细胞毒性（IC 50  <10μM）。有趣的是，大多数衍生物（8a – l和13a – l）显示出比其前体（7a – d和12a – d）增强的活性，这表明二硫代氨基甲酸酯与β-咔啉的组合可增强8a – l和8a – l的细胞毒性。13a – l。此外，导数8j和13g在DU-145癌细胞上显示出显着的细胞毒性活性，IC 50值分别为1.34μM和0.79μM。此外，通过膜联蛋白V-FITC和Hoechst染色测定法证实了这些衍生
• Synthesis and in vitro cytotoxic evaluation of novel 3,4,5-trimethoxyphenyl substituted β-carboline derivatives
  作者：Qifeng Wu、Rihui Cao、Manxiu Feng、Xiangdong Guan、Chunming Ma、Jinbing Liu、Huacan Song、Wenlie Peng

  DOI：10.1016/j.ejmech.2008.03.030

  日期：2009.2

  To elucidate further our SARs' study on the chemistry and cytotoxic activity and probe the structural requirement for the potent antitumor activity of beta-carbolines, a series of novel 1,9-disubstituted and 1,3,9-trisubstituted beta-carboline derivatives were designed and synthesized from the starting material L-tryptophan and 3,4,5-trimethoxybenezaldehyde. Cytotoxic activities of these compounds in vitro were investigated, and the SARs associated with position-1, 3 and 9 substituents in beta-carbolines have also been discussed. It has been observed that these compounds only displayed moderate to weak cytotoxic activities. Interestingly, most of the investigated compounds displayed selectively cytotoxic activities to human BCG-823 cell lines with IC50 value lower than 100 mu M. In addition, the short alkyl substituents in position-9 increased the cytotoxic activities with the tendency of n-butyl > ethyl > methyl. These data confirmed that (1) an alkyl substituent at position-9 of beta-carboline nucleus plays an important role in determining their antitumor activities; (2) different beta-carbolines bearing various substituents in beta-carboline nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects. (C) 2008 Elsevier Masson SAS. All fights reserved.