2-(3,6-二羟基-2,4-二甲氧基苯基)硫基乙酸 | 133735-47-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 2-(3,6-二羟基-2,4-二甲氧基苯基)硫基乙酸
• 英文名称: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid
• 英文别名: 2-(3,6-dihydroxy-2,4-dimethoxyphenyl)sulfanylacetic acid
• CAS: 133735-47-4
• 化学式: C₁₀H₁₂O₆S
• 分子量: 260.268
• InChiKey: ASIQVPPVPSRUQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(3,6-二羟基-2,4-二甲氧基苯基)硫基乙酸 、 (S)-2-[(S)-2-((S)-2-Amino-6-benzyloxycarbonylamino-hexanoylamino)-5-guanidino-pentanoylamino]-5-guanidino-pentanoic acid methyl ester; compound with trifluoro-acetic acid 在 五氟苯酚 、 N,N'-二环己基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成 DMQ-MA-Lys(Cbz)-Arg-Arg-OMe
  参考文献：
  名称：

  摘要：

  This paper reports a continuing study of the use of short-chain peptides as carriers of a potential anti-tumour agent, namely 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we have synthesized two new peptide-DMQ-MA conjugates: DMQ-MA-Lys(Cbz)-Arg-Arg-OMe and DMQ-MA-Lys(DMQ-MA)-Arg-OMe. These were synthesized by coupling protected amino acids using Pfp/N,N'-dicyclohexylcarbodiimide (Pfp = pentafluorophenol) in solution; the next conjugation was achieved by treatment with the pentafluorophenyl ester of DMQ-MA in dimethylformamide. We have investigated the DNA scission chemistry of these drugs, and the results show that they can cleave pBR322 DNA in concentrations as low as 5-40 muM without the addition of hydrogen peroxide or ultraviolet (UV) irradiation. The addition of a catalytic amount of ferrous ions has a significant enhancement on the DNA strand cleavage induced by the drugs: the cleavage degree increases with increasing time. Addition of hydroxyl radical scavengers such as dimethyl sulfoxide, glycerol, etc., significantly inhibits DNA strand cleavage. Oxidants with free-radical character are well known investigators of DNA damage. In order to explore the mechanism of DNA strand cleavage, we also investigated the reactive oxygen species. The active species produced by the drugs were studied using the Rhodamine B (Rhb) assay and electron paramagnetic resonance (EPR) spectroscopy. The results show fast production of the hydroxyl radical, which is trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the characteristic signal of DMPO . OH (1 : 2 : 2 : 1) is recorded. DNA binding constants determined by the ethidium bromide assay are approximately 10(4) M-1. The results of this study show that the degree of DNA scission is not related to the binding constants, nor is it related to the hydroxyl radical intensity data solely, but rather to the ability of the drugs to generate various free radicals.

  DOI：

  10.1071/ch01063

文献信息

• DNA Scission Chemistry and EPR Studies of Four New Bis(2,6-Dimethoxyhydroquinone - 3-Mercaptoacetic Acid) - Peptide Conjugates
  作者：Yu-Fei Song

  DOI：10.1071/ch03111

  日期：——

  In an effort to investigate the use of short peptide chains as carriers of new antitumour agents, four tripeptide cytotoxic agent conjugates, namely DMQ–MA–Lys(DMQ–MA)–Lys(Cbz)–Arg–OMe, DMQ–MA–Lys(DMQ–MA)–Phe–Arg–OMe, DMQ–MA–Lys(DMQ–MA)–Ile–Arg–OMe, and DMQ–MA–Lys(DMQ–MA)–Val–Arg–OMe, were synthesized. The cytotoxic agent conjugated to the N-terminal, and the ξ-amino group of lysine of the tripeptides

  为了研究使用短肽链作为新型抗肿瘤剂的载体，四种三肽细胞毒剂偶联物，即 DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-OMe、DMQ-MA-Lys (DMQ–MA)–Phe–Arg–OMe、DMQ–MA–Lys(DMQ–MA)–Ile–Arg–OMe 和 DMQ–MA–Lys(DMQ–MA)–Val–Arg–OMe 被合成。与 N 末端缀合的细胞毒剂和三肽赖氨酸的 ξ-氨基是 2,6-二甲氧基氢醌-3-巯基乙酸 (DMQ-MA)。根据 Pfp/DCC 方法（其中 Pfp 指五氟苯酚， DCC 指 N,N'-二环己基碳二亚胺），通过在溶液中偶联受保护的氨基酸残基来合成三肽。DNA 断裂化学表明，这些化合物能够在药物浓度低至 5–20 μM 的情况下将超螺旋 DNA 切割成开环形式，而无需添加 H2O2 或紫外线照射。当羟基自由基清除剂如甘油和苯甲酸钠加入反应体系时，DNA 切
• US4978783A
  申请人：——

  公开号：US4978783A

  公开（公告）日：1990-12-18
• ——
  作者：Yu-Fei Song、Pin Yang

  DOI：10.1071/ch01063

  日期：——

  This paper reports a continuing study of the use of short-chain peptides as carriers of a potential anti-tumour agent, namely 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we have synthesized two new peptide-DMQ-MA conjugates: DMQ-MA-Lys(Cbz)-Arg-Arg-OMe and DMQ-MA-Lys(DMQ-MA)-Arg-OMe. These were synthesized by coupling protected amino acids using Pfp/N,N'-dicyclohexylcarbodiimide (Pfp = pentafluorophenol) in solution; the next conjugation was achieved by treatment with the pentafluorophenyl ester of DMQ-MA in dimethylformamide. We have investigated the DNA scission chemistry of these drugs, and the results show that they can cleave pBR322 DNA in concentrations as low as 5-40 muM without the addition of hydrogen peroxide or ultraviolet (UV) irradiation. The addition of a catalytic amount of ferrous ions has a significant enhancement on the DNA strand cleavage induced by the drugs: the cleavage degree increases with increasing time. Addition of hydroxyl radical scavengers such as dimethyl sulfoxide, glycerol, etc., significantly inhibits DNA strand cleavage. Oxidants with free-radical character are well known investigators of DNA damage. In order to explore the mechanism of DNA strand cleavage, we also investigated the reactive oxygen species. The active species produced by the drugs were studied using the Rhodamine B (Rhb) assay and electron paramagnetic resonance (EPR) spectroscopy. The results show fast production of the hydroxyl radical, which is trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and the characteristic signal of DMPO . OH (1 : 2 : 2 : 1) is recorded. DNA binding constants determined by the ethidium bromide assay are approximately 10(4) M-1. The results of this study show that the degree of DNA scission is not related to the binding constants, nor is it related to the hydroxyl radical intensity data solely, but rather to the ability of the drugs to generate various free radicals.