2-methylthio-6-(2-hydroxybenzylamino)purine riboside | 722509-95-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-methylthio-6-(2-hydroxybenzylamino)purine riboside
• 英文别名: 2-methylthio-ortho-topolin riboside；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(2-hydroxyphenyl)methylamino]-2-methylsulfanylpurin-9-yl]oxolane-3,4-diol
• CAS: 722509-95-7
• 化学式: C₁₈H₂₁N₅O₅S
• 分子量: 419.461
• InChiKey: LVXPLZRHKKDEKC-LSCFUAHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  171
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (氨基甲基)-苯酚 、 2-Methylmercapto-6-chloro-9β-(D-ribofuranosyl)-purine 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以50.5%的产率得到2-methylthio-6-(2-hydroxybenzylamino)purine riboside
  参考文献：
  名称：

  Anticancer activity of natural cytokinins: A structure–activity relationship study

  摘要：

  Cytokinin ribosides (N(6)-substituted adenosine derivatives) have been shown to have anticancer activity both in vitro and in vivo. This study presents the first systematic analysis of the relationship between the chemical structure of cytokinins and their cytotoxic effects against a panel of human cancer cell lines with diverse histopathological origins. The results confirm the cytotoxic activity of N(6)-isopentenyladenosine, kinetin riboside, and N(6)-benzyladenosine and show that the spectrum of cell lines that are sensitive to these compounds and their tissues of origin are wider than previously reported. The first evidence that the hydroxylated aromatic cytokinins (ortho-, meta-, para-topolin riboside) and the isoprenoid cytokinin cis-zeatin riboside have cytotoxic activities is presented.Most cell lines in the panel showed greatest sensitivity to ortho-topolin riboside (IC(50) = 0.5-11.6 mu M). Cytokinin nucleotides, some synthesized for the first time in this study, were usually active in a similar concentration range to the corresponding ribosides. However, cytokinin free bases, 2-methylthio derivatives and both O- and N-glucosides showed little or no toxicity. Overall the study shows that structural requirements for cytotoxic activity of cytokinins against human cancer cell lines differ from the requirements for their activity in plant bioassays. The potent anticancer activity of ortho-topolin riboside (GI(50) = 0.07-84.60 mu M, 1st quartile = 0.33 mu M, median = 0.65 mu M, 3rd quartile = 1.94 mu M) was confirmed using NCI(60), a standard panel of 59 cell lines, originating from nine different tissues. Further, the activity pattern of oTR was distinctly different from those of standard anticancer drugs, suggesting that it has a unique mechanism of activity. In comparison with standard drugs, oTR showed exceptional cytotoxic activity against NCI(60) cell lines with a mutated p53 tumour suppressor gene. oTR also exhibited significant anticancer activity against several tumour models in in vivo hollow fibre assays. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.phytochem.2010.04.018

文献信息

• Anticancer activity of natural cytokinins: A structure–activity relationship study
  作者：Jiří Voller、Marek Zatloukal、René Lenobel、Karel Doležal、Tibor Béreš、Vladimír Kryštof、Lukáš Spíchal、Percy Niemann、Petr Džubák、Marián Hajdúch、Miroslav Strnad

  DOI：10.1016/j.phytochem.2010.04.018

  日期：2010.8

  Cytokinin ribosides (N(6)-substituted adenosine derivatives) have been shown to have anticancer activity both in vitro and in vivo. This study presents the first systematic analysis of the relationship between the chemical structure of cytokinins and their cytotoxic effects against a panel of human cancer cell lines with diverse histopathological origins. The results confirm the cytotoxic activity of N(6)-isopentenyladenosine, kinetin riboside, and N(6)-benzyladenosine and show that the spectrum of cell lines that are sensitive to these compounds and their tissues of origin are wider than previously reported. The first evidence that the hydroxylated aromatic cytokinins (ortho-, meta-, para-topolin riboside) and the isoprenoid cytokinin cis-zeatin riboside have cytotoxic activities is presented.Most cell lines in the panel showed greatest sensitivity to ortho-topolin riboside (IC(50) = 0.5-11.6 mu M). Cytokinin nucleotides, some synthesized for the first time in this study, were usually active in a similar concentration range to the corresponding ribosides. However, cytokinin free bases, 2-methylthio derivatives and both O- and N-glucosides showed little or no toxicity. Overall the study shows that structural requirements for cytotoxic activity of cytokinins against human cancer cell lines differ from the requirements for their activity in plant bioassays. The potent anticancer activity of ortho-topolin riboside (GI(50) = 0.07-84.60 mu M, 1st quartile = 0.33 mu M, median = 0.65 mu M, 3rd quartile = 1.94 mu M) was confirmed using NCI(60), a standard panel of 59 cell lines, originating from nine different tissues. Further, the activity pattern of oTR was distinctly different from those of standard anticancer drugs, suggesting that it has a unique mechanism of activity. In comparison with standard drugs, oTR showed exceptional cytotoxic activity against NCI(60) cell lines with a mutated p53 tumour suppressor gene. oTR also exhibited significant anticancer activity against several tumour models in in vivo hollow fibre assays. (C) 2010 Elsevier Ltd. All rights reserved.