1,1'-(1,5-pentanediyl)bis[thymine] | 31167-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,1'-(1,5-pentanediyl)bis[thymine]
• 英文别名: N1,N1’-(pentane-1,5-diyl)bis-thymine；1,1'-Pentamethylenbisthymin；5,5'-dimethyl-1H,1'H-1,1'-pentane-1,5-diyl-bis-pyrimidine-2,4-dione；5-Methyl-1-[5-(5-methyl-2,4-dioxopyrimidin-1-yl)pentyl]pyrimidine-2,4-dione；5-methyl-1-[5-(5-methyl-2,4-dioxopyrimidin-1-yl)pentyl]pyrimidine-2,4-dione
• CAS: 31167-32-5
• 化学式: C₁₅H₂₀N₄O₄
• 分子量: 320.348
• InChiKey: KHBJQWAVTOHLQT-UHFFFAOYSA-N

物化性质

• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1'-(1,5-pentanediyl)bis[thymine] 以 水 、 丙酮 为溶剂， 反应 2.0h， 以60%的产率得到
  参考文献：
  名称：

  Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

  摘要：

  我们在此报告合成了一种新型嘧啶类生物模拟光附加物，其在核碱基之间带有烷基间隔，并对过表达人类拓扑异构酶1（TOP1）的两种突变癌细胞系SKMEL28和RPMI7951表现出抗黑色素瘤活性。其中，Dewar价态光附加物的选择性指数高于相应的嘧啶-（6-4）-嘧啶酮和环丁烷对应物，并通过分子对接分析评估了其与TOP1/DNA复合物之间的最高亲和力。新型光附加物的抗黑色素瘤活性在载入UV光保护木质素纳米粒子作为稳定剂和高效药物输送系统后得以保留。总体而言，这些结果支持一种结合抗黑色素瘤和UV防晒策略，涉及使用光保护木质素纳米粒子对皮肤上的胸腺嘧啶二聚体进行控制释放，随后将其牺牲性转化为光附加物，并连续抑制黑色素瘤和警觉细胞UV机制修复途径。

  DOI：

  10.3390/ijms23020915
• 作为产物：
  描述：

  胸腺嘧啶 在 哌啶 作用下， 以 乙腈 为溶剂， 反应 100.0h， 生成 1,1'-(1,5-pentanediyl)bis[thymine]
  参考文献：
  名称：

  Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

  摘要：

  我们在此报告合成了一种新型嘧啶类生物模拟光附加物，其在核碱基之间带有烷基间隔，并对过表达人类拓扑异构酶1（TOP1）的两种突变癌细胞系SKMEL28和RPMI7951表现出抗黑色素瘤活性。其中，Dewar价态光附加物的选择性指数高于相应的嘧啶-（6-4）-嘧啶酮和环丁烷对应物，并通过分子对接分析评估了其与TOP1/DNA复合物之间的最高亲和力。新型光附加物的抗黑色素瘤活性在载入UV光保护木质素纳米粒子作为稳定剂和高效药物输送系统后得以保留。总体而言，这些结果支持一种结合抗黑色素瘤和UV防晒策略，涉及使用光保护木质素纳米粒子对皮肤上的胸腺嘧啶二聚体进行控制释放，随后将其牺牲性转化为光附加物，并连续抑制黑色素瘤和警觉细胞UV机制修复途径。

  DOI：

  10.3390/ijms23020915

文献信息

• NMR and UV Study of 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[thymine] and 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[uracil]
  作者：Toshio Itahara

  DOI：10.1246/bcsj.70.2239

  日期：1997.9

  Treatment of thymine or uracil with Br(CH2)nBr (n = 3—10) in the presence of t-BuOK gave 1,1′-(α,ω-alkanediyl)bis[thymine] or 1,1′-(α,ω-alkanediyl)bis[uracil] together with 1-(ω-bromoalkyl)thymine or 1-(ω-bromoalkyl)uracil. The structures of these products were determined on the basis of the coupling constants between 5- and 3-positions of uracil ring on the 1H NMR spectra. Molecular aggregation of the thymine and uracil rings of these compounds in aqueous solution was studied on the basis of their 1H NMR and UV spectra. A stacking interaction of the two thymine rings linked by shorter polymethylene chains such as trimethylene and tetramenthylene groups was observed.

  将胸腺嘧啶或尿嘧啶与Br(CH2)nBr（n = 3—10）在t-BuOK存在下处理，得到了1,1′-(α,ω-烷烃二基)双[胸腺嘧啶]或1,1′-(α,ω-烷烃二基)双[尿嘧啶]，以及1-(ω-溴烷基)胸腺嘧啶或1-(ω-溴烷基)尿嘧啶。这些产物的结构是基于尿嘧啶环中5位和3位之间的耦合常数在1H NMR光谱上的分析来确定的。基于它们的1H NMR和紫外光谱，研究了这些化合物在水溶液中胸腺嘧啶和尿嘧啶环的分子聚集情况。观察到由较短的聚亚 methylene 链（如三亚甲基和四亚甲基基团）连接的两个胸腺嘧啶环之间存在堆叠相互作用。
• Photoprotection of DNA (in vitro) by acyclothymidine dinucleosides
  作者：Abbas Raza、Christine D. Dreis、Robert Vince

  DOI：10.1016/j.bmcl.2012.12.023

  日期：2013.2

  Excessive exposure to sunlight is primarily implicated in ultraviolet (UV) induced skin cancers worldwide. Direct absorption of UV radiation by DNA leads to the formation of cyclobutane pyrimidine dimers (CPDs) resulting in DNA damage. The molecular mechanisms involved in the mutagenicity of CPDs are well established. Photoprotection of the skin from the detrimental effects of UV is essential in preventing skin damage. A variety of formulations, which essentially contain UV filters have been used as photoprotective agents of the skin. These comprise aromatic and inorganic molecules, whose mechanism of action involves either absorption, reflection, or scattering of UV radiation. However, the downstream photoproducts of some of these molecules have undesirable characteristics which compromise their utility. A biomimetic approach involving structural analogs of nucleic acids can help overcome these limitations. Herein, we show the photoprotective action of acyclothymidine dinucleosides on both plasmid and cellular DNA. Published by Elsevier Ltd.
• Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity
  作者：Sofia Gabellone、Davide Piccinino、Silvia Filippi、Tiziana Castrignanò、Claudio Zippilli、Davide Del Buono、Raffaele Saladino

  DOI：10.3390/ijms23020915

  日期：——

  We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

  我们在此报告合成了一种新型嘧啶类生物模拟光附加物，其在核碱基之间带有烷基间隔，并对过表达人类拓扑异构酶1（TOP1）的两种突变癌细胞系SKMEL28和RPMI7951表现出抗黑色素瘤活性。其中，Dewar价态光附加物的选择性指数高于相应的嘧啶-（6-4）-嘧啶酮和环丁烷对应物，并通过分子对接分析评估了其与TOP1/DNA复合物之间的最高亲和力。新型光附加物的抗黑色素瘤活性在载入UV光保护木质素纳米粒子作为稳定剂和高效药物输送系统后得以保留。总体而言，这些结果支持一种结合抗黑色素瘤和UV防晒策略，涉及使用光保护木质素纳米粒子对皮肤上的胸腺嘧啶二聚体进行控制释放，随后将其牺牲性转化为光附加物，并连续抑制黑色素瘤和警觉细胞UV机制修复途径。