gold(1+);2-(2-phenyl-3-pyridin-2-yl-4,5,6,7-tetrahydroisophosphindol-1-yl)pyridine;(2S,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate | 1111864-58-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: gold(1+);2-(2-phenyl-3-pyridin-2-yl-4,5,6,7-tetrahydroisophosphindol-1-yl)pyridine;(2S,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate
• CAS: 1111864-58-4
• 化学式: C₃₈H₄₀AuN₂O₉PS
• 分子量: 928.75
• InChiKey: VBTOSOBJGKCXRQ-SUZXOXMZSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.28
• 重原子数：
  52
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  141
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1-phenyl-2,5-bis(2-pyridyl)phosphole gold chloride 、 1-硫代-b-D-葡萄糖四乙酸酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以70%的产率得到gold(1+);2-(2-phenyl-3-pyridin-2-yl-4,5,6,7-tetrahydroisophosphindol-1-yl)pyridine;(2S,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate
  参考文献：
  名称：

  Antiglioma activity of GoPI-sugar, a novel gold(I)–phosphole inhibitor: Chemical synthesis, mechanistic studies, and effectiveness in vivo

  摘要：

  Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-beta-D-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430 mu M, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3 nM) and human glutathione reductase (IC50 88.5 nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2014.01.006