N¹,N⁴,N⁸-tris(mesitylenesulfonyl)spermidine | 189340-47-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N¹,N⁴,N⁸-tris(mesitylenesulfonyl)spermidine
• 英文别名: 2,4,6-trimethyl-N-[4-[(2,4,6-trimethylphenyl)sulfonyl-[3-[(2,4,6-trimethylphenyl)sulfonylamino]propyl]amino]butyl]benzenesulfonamide
• CAS: 189340-47-4
• 化学式: C₃₄H₄₉N₃O₆S₃
• 分子量: 691.978
• InChiKey: MZUDHBLZGIDWKR-UHFFFAOYSA-N

物化性质

• 沸点：
  819.0±75.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N¹,N⁴,N⁸-tris(mesitylenesulfonyl)spermidine 在 氢溴酸 、 sodium hydride 、 苯酚 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 反应 36.5h， 生成 2,6-二甲基二苯并[b,d]噻吩
  参考文献：
  名称：

  A Comparison of Structure−Activity Relationships between Spermidine and Spermine Analogue Antineoplastics

  摘要：

  A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N-1-acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of-the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N-alpha,N-omega-substituents. It appears that there is an optimum chain length for various activities and that the larger the N-alpha,N-omega-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.

  DOI：

  10.1021/jm960849j
• 作为产物：
  描述：

  2,4,6-三甲基苯磺酰氯 、 亚精胺 在 吡啶 作用下， 反应 4.0h， 生成 N¹,N⁴,N⁸-tris(mesitylenesulfonyl)spermidine
  参考文献：
  名称：

  The synthesis and the in vitro cytotoxicity studies of bisnaphthalimidopropyl polyamine derivatives against colon cancer cells and parasite Leishmania infantum

  摘要：

  Bisnaphthalimidopropyl derivatives (BNIPSpd, BNIPDaoct, BNIPDanon, BNIPDadec, BNIPDpta and BNIPDeta) were synthesised in yields ranging from 50% to 70% and their cytotoxicity against colon cancer cells (Caco-2) and the parasite Leishmania infantum determined using the MTT assay. Cytotoxicity within Caco-2 cells was manifested with IC50 values between 0.3 and 22 mu M. Compounds with the central longer alkyl chains exhibited the highest cytotoxicity. Against L. infantum, IC50 values were encompassed within a narrower concentration range of 0.47-1.54 mu M. In the parasites, the presence of nitrogen in the central chain and the length of the central alkyl chains did not especially enhance cytotoxicity. This may be due to the way these compounds are transported in the cells. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.031

文献信息

• Synthesis and biological activities of bisnaphthalimido polyamines derivatives: cytotoxicity, DNA binding, DNA damage and drug localization in breast cancer MCF 7 cells
  作者：Anne-Marie Dance、Lynda Ralton、Zoe Fuller、Lesley Milne、Susan Duthie、Charles S. Bestwick、Paul Kong Thoo Lin

  DOI：10.1016/j.bcp.2004.09.020

  日期：2005.1

  New bisoxynaphthalimidopolyamines (BNIPOPut, BNIPOSpd and BNIPOSpm) were synthesized. Their cytotoxic properties were evaluated against breast cancer MCF 7 cells and compared with bisnaphthalimidopolyamines BNIPSpd and BNIPSpm. Among the bisoxynaphthalimido polyamines, BNIPOSpm and BNIPOSpd exhibited cytotoxic activity with an IC50 of 29.55 and 27.22 muM, respectively, while BNIPOPut failed to exert significant cytotoxicity after 48-h drug exposure. DNA binding was determined by midpoint of thermal denaturation (T-m) measurement, ethidium bromide displacement and DNA gel mobility. Both BNIPOSpm and BNIPOSpd exhibited strong binding affinities with DNA. BNIPOPut had the least effect. The results were compared with other cytotoxic bisnaphthalimido compounds (BNIPSpm and BNIPSpd) previously reported by us. Using the single cell gel electrophoresis assay, it was found that BNIPSpm and BNIPSpd caused substantial DNA damage to MCF 7 treated cells while BNIPOSpm showed no significant effect over a range of drug concentrations after 4-h drug exposure. However, after 12-h drug exposure, BNIPOSpm had induced significant DNA damage similar to that of BNIPSpm (after 4-h drug exposure). Fluorescence microscopic analysis revealed that at 1 muM drug concentration and after 6-h drug exposure, both BNIPSpm and BNIPSpd were located within the cell while the presence of BNIPOSpm, was not observed. Therefore, we conclude that BNIPSpd, BNIPSpm and BNIPOSpm induce DNA damage consistent with their rate of uptake into the cells. (C) 2004 Elsevier Inc. All rights reserved.
• The synthesis and the in vitro cytotoxicity studies of bisnaphthalimidopropyl polyamine derivatives against colon cancer cells and parasite Leishmania infantum
  作者：João Oliveira、Lynda Ralton、Joana Tavares、Anabela Codeiro-da-Silva、Charles S. Bestwick、Anne McPherson、Paul Kong Thoo Lin

  DOI：10.1016/j.bmc.2006.09.031

  日期：2007.1.1

  Bisnaphthalimidopropyl derivatives (BNIPSpd, BNIPDaoct, BNIPDanon, BNIPDadec, BNIPDpta and BNIPDeta) were synthesised in yields ranging from 50% to 70% and their cytotoxicity against colon cancer cells (Caco-2) and the parasite Leishmania infantum determined using the MTT assay. Cytotoxicity within Caco-2 cells was manifested with IC50 values between 0.3 and 22 mu M. Compounds with the central longer alkyl chains exhibited the highest cytotoxicity. Against L. infantum, IC50 values were encompassed within a narrower concentration range of 0.47-1.54 mu M. In the parasites, the presence of nitrogen in the central chain and the length of the central alkyl chains did not especially enhance cytotoxicity. This may be due to the way these compounds are transported in the cells. (c) 2006 Elsevier Ltd. All rights reserved.
• A Comparison of Structure−Activity Relationships between Spermidine and Spermine Analogue Antineoplastics
  作者：Raymond J. Bergeron、Yang Feng、William R. Weimar、James S. McManis、Hristina Dimova、Carl Porter、Brian Raisler、Otto Phanstiel

  DOI：10.1021/jm960849j

  日期：1997.5.1

  A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N-1-acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of-the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N-alpha,N-omega-substituents. It appears that there is an optimum chain length for various activities and that the larger the N-alpha,N-omega-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.