triphenyl (12-((3,4,5-trihydroxybenzoyl)oxy)dodecyl)phosphonium bromide | 1581234-56-1

• 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: triphenyl (12-((3,4,5-trihydroxybenzoyl)oxy)dodecyl)phosphonium bromide
• 英文别名: triphenyl(12-((3,4,5-trihydroxybenzoyl)oxy)-dodecyl)phosphonium bromide；triphenyl(12-((3,4,5-trihydroxybenzoyl)oxy)dodecyl)phosphonium bromide；Triphenyl-[12-(3,4,5-trihydroxybenzoyl)oxydodecyl]phosphanium;bromide；triphenyl-[12-(3,4,5-trihydroxybenzoyl)oxydodecyl]phosphanium;bromide
• CAS: 1581234-56-1
• 化学式: Br*C₃₇H₄₄O₅P
• 分子量: 679.631
• InChiKey: LOXNSJKDIPSPOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.86
• 重原子数：
  44
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  没食子酸 、 (12-hydroxydodecyl)triphenylphosphonium bromide 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以39%的产率得到triphenyl (12-((3,4,5-trihydroxybenzoyl)oxy)dodecyl)phosphonium bromide
  参考文献：
  名称：

  Antiproliferative and Uncoupling Effects of Delocalized, Lipophilic, Cationic Gallic Acid Derivatives on Cancer Cell Lines. Validation in Vivo in Singenic Mice

  摘要：

  Tumor cells principally exhibit increased mitochondrial transmembrane potential (ΔΨ(m)) and altered metabolic pathways. The therapeutic targeting and delivery of anticancer drugs to the mitochondria might improve treatment efficacy. Gallic acid exhibits a variety of biological activities, and its ester derivatives can induce mitochondrial dysfunction. Four alkyl gallate triphenylphosphonium lipophilic cations were synthesized, each differing in the size of the linker chain at the cationic moiety. These derivatives were selectively cytotoxic toward tumor cells. The better compound (TPP(+)C10) contained 10 carbon atoms within the linker chain and exhibited an IC50 value of approximately 0.4-1.6 μM for tumor cells and a selectivity index of approximately 17-fold for tumor compared with normal cells. Consequently, its antiproliferative effect was also assessed in vivo. The oxygen consumption rate and NAD(P)H oxidation levels increased in the tumor cell lines (uncoupling effect), resulting in a ΔΨ(m) decrease and a consequent decrease in intracellular ATP levels. Moreover, TPP(+)C10 significantly inhibited the growth of TA3/Ha tumors in mice. According to these results, the antineoplastic activity and safety of TPP(+)C10 warrant further comprehensive evaluation.

  DOI：

  10.1021/jm500174v

文献信息

• Antiproliferative and Uncoupling Effects of Delocalized, Lipophilic, Cationic Gallic Acid Derivatives on Cancer Cell Lines. Validation in Vivo in Singenic Mice
  作者：José A. Jara、Vicente Castro-Castillo、Jorge Saavedra-Olavarría、Liliana Peredo、Mario Pavanni、Fabián Jaña、María Eugenia Letelier、Eduardo Parra、María Inés Becker、Antonio Morello、Ulrike Kemmerling、Juan Diego Maya、Jorge Ferreira

  DOI：10.1021/jm500174v

  日期：2014.3.27

  Tumor cells principally exhibit increased mitochondrial transmembrane potential (ΔΨ(m)) and altered metabolic pathways. The therapeutic targeting and delivery of anticancer drugs to the mitochondria might improve treatment efficacy. Gallic acid exhibits a variety of biological activities, and its ester derivatives can induce mitochondrial dysfunction. Four alkyl gallate triphenylphosphonium lipophilic cations were synthesized, each differing in the size of the linker chain at the cationic moiety. These derivatives were selectively cytotoxic toward tumor cells. The better compound (TPP(+)C10) contained 10 carbon atoms within the linker chain and exhibited an IC50 value of approximately 0.4-1.6 μM for tumor cells and a selectivity index of approximately 17-fold for tumor compared with normal cells. Consequently, its antiproliferative effect was also assessed in vivo. The oxygen consumption rate and NAD(P)H oxidation levels increased in the tumor cell lines (uncoupling effect), resulting in a ΔΨ(m) decrease and a consequent decrease in intracellular ATP levels. Moreover, TPP(+)C10 significantly inhibited the growth of TA3/Ha tumors in mice. According to these results, the antineoplastic activity and safety of TPP(+)C10 warrant further comprehensive evaluation.