tris(1-ethyl-1H-indol-3-yl)methylium methanesulfonate | 1254174-01-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tris(1-ethyl-1H-indol-3-yl)methylium methanesulfonate
• 英文别名: 1-Ethyl-3-[(1-ethylindol-1-ium-3-ylidene)-(1-ethylindol-3-yl)methyl]indole;methanesulfonate
• CAS: 1254174-01-0
• 化学式: CH₃O₃S*C₃₁H₃₀N₃
• 分子量: 539.698
• InChiKey: HMEUUBYJMIBFNI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.79
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  78.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  tris(1H-indol-3-yl)methane 在 iron(III) chloride 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 水 、 二甲基亚砜 为溶剂， 反应 28.5h， 生成 tris(1-ethyl-1H-indol-3-yl)methylium methanesulfonate
  参考文献：
  名称：

  Tris(1-alkylindol-3-yl)methylium salts as a novel class of antitumor agents

  摘要：

  获得了三(1-烷基吲哚-3-基)甲烷，并将其氧化成三(1-烷基吲哚-3-基)甲盐类。生成的盐类对培养的肿瘤细胞的毒性比对非肿瘤细胞的毒性更大。三(1-烷基吲哚-3-基)甲基盐的细胞毒性取决于杂环 N 原子上取代基的长度，从 N-未取代衍生物到 N-丁基和 N-戊基衍生物。进一步增加 N-烷基取代基的长度会降低细胞毒性。三（1-烷基吲哚-3-基）甲基盐对肿瘤细胞的细胞毒性与其抗菌和抗真菌活性相关。三(1-烷基吲哚-3-基)甲基盐对革兰氏阳性微生物有杀灭细胞的作用，而活性最强的化合物对革兰氏阴性微生物也有杀灭细胞的作用。在各种肿瘤细胞、细菌和真菌中观察到的 N-烷基化三（吲哚-3-基）甲基衍生物结构-活性关系的相似模式表明，这些化合物诱导原核细胞和真核细胞死亡的机制具有普遍性。

  DOI：

  10.1007/s11172-010-0386-7

文献信息

• Synthesis and cytotoxic potency of novel tris(1-alkylindol-3-yl)methylium salts: Role of N-alkyl substituents
  作者：Sergey N. Lavrenov、Yuriy N. Luzikov、Evgeniy E. Bykov、Marina I. Reznikova、Evgenia V. Stepanova、Valeria A. Glazunova、Yulia L. Volodina、Victor V. Tatarsky、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.bmc.2010.07.025

  日期：2010.9

  Novel derivatives of tris(indol-3-yl)methane and tris(indol-3-yl)methylium salts with the alkyl substituents at the N-atoms of the indole rings were synthesized. An easy substitution of indole rings in trisindolylmethanes for other indoles under the action of acids is demonstrated, and the mechanism of substitution is discussed. To obtain trisindolylmethylium salts, the environmentally safe method of oxidation of trisindolylmethanes with air oxygen in acidic conditions was developed. Tris(1-alkylindol-3-yl)methanes and tris(1-alkylindol-3-yl)methylium salts represent three-bladed molecular propellers whose physico-chemical and biological properties strongly depend on the N-alkyl substituent. The cytotoxicity of novel compounds increased with the number of C atoms in the alkyl chains, with optimal number n = 3-5 whereas the derivatives with longer side chains were less cytotoxic. The most potent novel compounds killed human tumor cells at nanomolar-to-submicromolar concentrations, being one order of magnitude more potent than the prototype antibiotic turbomycin A [tris(indol-3-yl) methylium salt]. Apoptosis in HCT116 colon carcinoma cell line induced by tris(1-pentyl-1H-indol-3-yl) methylium methanesulfonate was detectable at concentrations tolerable by normal blood lymphocytes. Thus, N-alkyl substituted tris(1-alkylindol-3-yl) methylium salts emerge as perspective anticancer drug candidates. (C) 2010 Elsevier Ltd. All rights reserved.
• Tris(1-alkylindol-3-yl)methylium salts as a novel class of antitumor agents
  作者：E. V. Stepanova、A. A. Shtil’、S. N. Lavrenov、V. M. Bukhman、A. N. Inshakov、E. P. Mirchink、A. S. Trenin、O. A. Galatenko、E. B. Isakova、V. A. Glazunova、L. G. Dezhenkova、E. Sh. Solomko、E. E. Bykov、M. N. Preobrazhenskaya

  DOI：10.1007/s11172-010-0386-7

  日期：2010.12

  Tris(1-alkylindol-3-yl)methanes were obtained and oxidized into tris(1-alkylindol-3-yl)methylium salts. The resulting salts are more toxic to cultured tumor cells than to non-tumor ones. The cytotoxicity of tris(1-alkylindol-3-yl)methylium salts depends on the length of the substituent at the N atom of the heterocycle, increasing from an N-unsubstituted derivative toward N-butyl- and N-pentyl derivatives. A further increase in the length of the N-alkyl substituent lowers the cytotoxicity. The cytotoxicity of tris(1-alkylindol-3-yl)methylium salts for tumor cells correlates with their antibacterial and antifungal activity. Tris(1-alkylindol-3-yl)methylium salts produced a cytocide effect on Gram-positive microorganisms and the most active compounds, on Gram-negative microorganisms as well. Similar patterns of the structure—activity relationship of N-alkylated tris(indol-3-yl)methylium derivatives, which was observed for various lines of tumor cells, bacteria, and fungi, suggest the general character of the mechanisms of the death of prokaryotic and eukaryotic cells induced by these compounds.

  获得了三(1-烷基吲哚-3-基)甲烷，并将其氧化成三(1-烷基吲哚-3-基)甲盐类。生成的盐类对培养的肿瘤细胞的毒性比对非肿瘤细胞的毒性更大。三(1-烷基吲哚-3-基)甲基盐的细胞毒性取决于杂环 N 原子上取代基的长度，从 N-未取代衍生物到 N-丁基和 N-戊基衍生物。进一步增加 N-烷基取代基的长度会降低细胞毒性。三（1-烷基吲哚-3-基）甲基盐对肿瘤细胞的细胞毒性与其抗菌和抗真菌活性相关。三(1-烷基吲哚-3-基)甲基盐对革兰氏阳性微生物有杀灭细胞的作用，而活性最强的化合物对革兰氏阴性微生物也有杀灭细胞的作用。在各种肿瘤细胞、细菌和真菌中观察到的 N-烷基化三（吲哚-3-基）甲基衍生物结构-活性关系的相似模式表明，这些化合物诱导原核细胞和真核细胞死亡的机制具有普遍性。