2-(anthracen-10-yl-methyl)-1,2,3,4-tetrahydro-β-carboline | 1620100-03-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 2-(anthracen-10-yl-methyl)-1,2,3,4-tetrahydro-β-carboline
• 英文别名: 2-(Anthracen-9-ylmethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole；2-(anthracen-9-ylmethyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole
• CAS: 1620100-03-9
• 化学式: C₂₆H₂₂N₂
• 分子量: 362.474
• InChiKey: HOIQAWOYXGHYDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  1,2,3,4-四氢-9H-吡啶[3,4-B]并吲哚 、 9-氯甲基蒽 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以66%的产率得到2-(anthracen-10-yl-methyl)-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines

  摘要：

  A series of N-substituted tetrahydro-beta-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 mu M, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 mu M, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 mu M. Several analogs also displayed antitrypanosomal activity against Tiypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 mu M, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.06.030

文献信息

• Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines
  作者：Sudhakar Manda、Shabana I. Khan、Surendra K. Jain、Shabber Mohammed、Babu L. Tekwani、Ikhlas A. Khan、Ram A. Vishwakarma、Sandip B. Bharate

  DOI：10.1016/j.bmcl.2014.06.030

  日期：2014.8

  A series of N-substituted tetrahydro-beta-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 mu M, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 mu M, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 mu M. Several analogs also displayed antitrypanosomal activity against Tiypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 mu M, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages). (C) 2014 Elsevier Ltd. All rights reserved.
• Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishment of its structure–activity relationship
  作者：Sudhakar Manda、Sadhana Sharma、Abubakar Wani、Prashant Joshi、Vikas Kumar、Santosh K. Guru、Sonali S. Bharate、Shashi Bhushan、Ram A. Vishwakarma、Ajay Kumar、Sandip B. Bharate

  DOI：10.1016/j.ejmech.2015.10.049

  日期：2016.1

  The screening of IIIM natural products repository for P-gp modulatory activity in P-gp over-expressing human adenocarcinoma LS-180 cells led to the identification of 7 natural products viz. withaferin, podophyllotoxin, 3-demethylcolchicine, agnuside, reserpine, seseberecine and fascaplysin as P-gp inducers. Fascaplysin (6a), a marine-derived bis-indole alkaloid, was the most potent among all of them, showing induction of P-gp with EC50 value of 25 nM. P-gp induction is one of the recently targeted strategy to increase amyloid-beta clearance from Alzheimer brains. Thus, we pursued a medicinal chemistry of fascaplysin to establish its structure activity relationship for P-gp induction activity. Four series of analogs viz, substituted quaternary fascaplysin analogs, D-ring opened quaternary analogs, D-ring opened non-quaternary analogs, and beta-carbolinium analogs were synthesized and screened for P-gp induction activity. Among the total of 48 analogs screened, only quaternary nitrogen containing analogs 6a-g and 10a, 10h-1 displayed promising P-gp induction activity; whereas non-planar non-quaternary analogs 9a-m, 13a-n, 15a-h were devoid of this activity. The P-gp induction activity of best compounds was then confirmed by western-blot analysis, which indicated that fascaplysin (6a) along with 4,5-difluoro analog of fascaplysin 6f and D-ring opened analog 10j displayed 4-8 fold increase in P-gp expression in LS-180 cells at 1 mu M. Additionally, compounds 6a and 6f also showed inhibition of acetylcholinestease (AChE), an enzyme responsible for neuronal loss in Alzheimer's disease. Thus, fascaplysin and its analogs showing promising P-gp induction along with AChE inhibition at 1 mu M, with good safety window (LS-180: IC50 > 10 mu M, hGF: 4 mu M), clearly indicates their promise for development as an anti-Alzheimer agent. (C) 2015 Elsevier Masson SAS. All rights reserved.