2-(4-(trifluoromethylphenyl)-1H-imidazo[4,5f][1,10]phenanthroline) | 1233850-88-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(4-(trifluoromethylphenyl)-1H-imidazo[4,5f][1,10]phenanthroline)
• 英文别名: 2-(4-trifluoromethylphenyl)imidazole[4,5-f][1,10]phenanthroline；2-(4-trifluoromethylphenyl)-imidazo[4,5f][1,10]phenanthroline；p-CFPIP；2-[4-(Trifluoromethyl)phenyl]-1,3,7,8-tetraaza-1H-cyclopenta[l]phenanthrene；2-[4-(trifluoromethyl)phenyl]-1H-imidazo[4,5-f][1,10]phenanthroline
• CAS: 1233850-88-8
• 化学式: C₂₀H₁₁F₃N₄
• 分子量: 364.329
• InChiKey: RCRGNBYQYKKXMP-UHFFFAOYSA-N

物化性质

• 沸点：
  586.8±60.0 °C(Predicted)
• 密度：
  1.465±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [RuCl2(benzene)]2 、 2-(4-(trifluoromethylphenyl)-1H-imidazo[4,5f][1,10]phenanthroline) 以 二氯甲烷 为溶剂， 反应 0.5h， 以91.3%的产率得到
  参考文献：
  名称：

  Microwave-assisted synthesis of arene ruthenium(II) complexes that induce S-phase arrest in cancer cells by DNA damage-mediated p53 phosphorylation

  摘要：

  A series of arene ruthenium(II) complexes coordinated by phenanthroimidazole derivates, [(C6H6)Ru(L) Cl]Cl center dot 2H(2)O (1b L = IP, 2b L = p-NMe2PIP, 3b L = p-MeOPIP, 4b L = p-HOPIP, 5b L = p-COOHPIP, 6b L = p-CF3PIP, 7b L = p-BrPIP) have been synthesized in yields of 89-92% under microwave irradiation in 30 min, and the crystal structure of 1b by XRD gives a typical "piano stool" conformation. The antitumor activity of these complexes against various tumor cells have been evaluated by MTT assay, and the results show that this type of arene Ru(II) complexes exhibit acceptable inhibitory effect against all of these tumor cells, especially osteosarcoma MG-63 cells, but with low toxicity toward HK-2 human normal cells. Studies on the mechanism revealed that cell cycle arrest at S-phase in MG-63 cells induced by the arene Ru(II) complex 2b, which was confirmed by the increase in the percentage of cells at S-phase and down-regulator of cyclin A. The further studies by Comet assay at single cell level indicated that DNA damage in MG-63 cells was triggered by 2b, following with the up-regulation of phosphorylated p53 and histone. The studies by spectroscopy in vitro also indicate that 2b bind to DNA molecule by intercalative mode to disturb the bio-function of tumor cells. In conclusion, the synthetic arene Ru(II) complexes could serve as novel p53 activator with potential application in cancer chemotherapy. (c) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.037
• 作为产物：
  描述：

  1,10-菲罗啉 在 硫酸 、 ammonium acetate 、 硝酸 、 potassium bromide 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 生成 2-(4-(trifluoromethylphenyl)-1H-imidazo[4,5f][1,10]phenanthroline)
  参考文献：
  名称：

  咪唑并[4,5 f ] [1,10]菲咯啉衍生物通过NF-κB途径抑制A549细胞c-myc基因表达

  摘要：

  1,10-菲咯啉已显示出抗癌活性。在这里，合成了一系列咪唑并[4,5 f ] [1,10]菲咯啉衍生物1-10，并进一步阐明了它们的生物学活性。我们发现2-（4-溴苯基）-咪唑并[4,5 f ] [1,10]菲咯啉（化合物3）在使用3-（4,5-二甲基-2 -噻唑基）-2,5-二苯基溴化四氮唑（MTT）分析。流式细胞仪分析显示，化合物3通过人肺腺癌细胞系A549的凋亡和坏死诱导。此外，化合物3这种治疗导致A549细胞中IκBα的上调以及p65和c-myc的下调。综上所述，这些结果表明化合物3通过抑制NF-κB活性和下调c-myc基因表达来抑制细胞增殖，并且可能作为人癌症，尤其是肺癌的化学预防和化学治疗剂而进一步评估的候选者。癌症。

  DOI：

  10.1016/j.bmcl.2011.11.063

文献信息

• 一种芳烃钌配合物及其制备方法与应用
  申请人：广东药科大学

  公开号：CN107793454B

  公开（公告）日：2020-05-05

  本发明公开了一种芳烃钌配合物，采用R1R2R3PIP为主配体，所述R1、R2、R3独立地选自‑Cl,‑F,‑Br,‑I,‑CF3,‑NO2,‑OCH3,‑OH,‑COOH,‑CH3,‑N(CH3)2,‑C2H2,‑SO2CH3、碳原子数为1～6的烷基或碳原子为1～6的取代烷基、吡啶基或取代吡啶基、呋喃基或取代呋喃基、吡咯基或取代吡咯基、噻唑或取代噻唑基；其中，所述苯基、吡啶基、呋喃基、噻唑的取代基均独立的选自羟基、硝基、卤素、氨基、羧基、氰基、巯基、碳原子数为3～8的环烷基、SO3H、碳原子数为1～6的烷基、碳原子数为2～6的链烯基、碳原子为2～6的链炔基、羟基(C1‑C6)烷基、氨基(C1‑C6)烷基、CO2R’、CONR’R’、COR’、SO2R’R’、(C1‑C6)烷氧基、(C1‑C6)烷硫基、‑N＝NR’、NR’R’或三氟(C1‑C6)烷基中的任一种。
• Cyclometalated Iridium(III) Imidazole Phenanthroline Complexes as Luminescent and Electrochemiluminescent G-Quadruplex DNA Binders
  作者：Katherine J. Castor、Kimberly L. Metera、Ushula M. Tefashe、Christopher J. Serpell、Janine Mauzeroll、Hanadi F. Sleiman

  DOI：10.1021/acs.inorgchem.5b00921

  日期：2015.7.20

  Six cyclometalated iridium(III) phenanthroimidazole complexes with different modifications to the imidazole phenanthroline ligand exhibit enhanced luminescence when bound to guanine (G-) quadruplex DNA sequences. The complexes bind with low micromolar affinity to human telomeric and c-myc sequences in a 1:1 complex:quadruplex stoichiometry. Due to the luminescence enhancement upon binding to G-quadruplex

  当与鸟嘌呤（G-）四重体DNA序列结合时，对咪唑菲咯啉配体具有不同修饰的六个环金属化铱（III）菲并咪唑配合物显示出增强的发光。配合物以低的微摩尔亲和力与人端粒和c-myc序列以1：1配合物：四链体化学计量比结合。由于与G-四链体DNA结合时的发光增强，因此该复合体可用作选择性四链体指示剂。另外，在特定的G-四链体序列存在下，所有复合物的电化学发光都增加，证明了开发基于ECL的G-四链体测定的潜力。
• Studies on characterization, telomerase inhibitory properties and G-quadruplex binding of η⁶-arene ruthenium complexes with 1,10-phenanthroline-derived ligands
  作者：Dongdong Sun、Rong Zhang、Fang Yuan、Du Liu、Yanhui Zhou、Jie Liu

  DOI：10.1039/c1dt11676b

  日期：——

  Two arene ruthenium complexes [Ru(η6-C6H6)(p-MOPIP)Cl]+1 and [Ru(η6-C6H6)(p-CFPIP)Cl]+2, where p-MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5f][1,10] phenanthroline and p-CFPIP = 2-(4-trifluoromethylphenyl)-imidazo[4,5f][1,10] phenanthroline, were prepared and the interactions of these compounds with DNA oligomers 5′-G3(T2AG3)3-3′(HTG21) have been studied by UV-vis and circular dichroism (CD) spectroscopy, gel mobility shift assay, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay and telomeric repeat amplification protocol (TRAP) assay. The results show that both complexes can induce the stabilization of quadruplex DNA but complex 1 is a better G-quadruplex binder than complex 2. The two ruthenium complexes tested led to an inhibition of the enzyme telomerase and complex 1 was the significantly better inhibitor. A novel visual method has been developed for making a distinction between G-quadruplex DNA and double DNA by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. Furthermore, in vitro cytotoxicity studies showed complex 1 exhibited quite potent antitumor activities and the greatest inhibitory selectivity against cancer cell lines.

  两种芳香族钌配合物 [Ru(η6-C6H6)(p-MOPIP)Cl]⁺1 和 [Ru(η6-C6H6)(p-CFPIP)Cl]⁺2 被合成，其中 p-MOPIP = 2-(4-甲氧基苯基)-咪唑[4,5f][1,10]菲啰啉，p-CFPIP = 2-(4-三氟甲基苯基)-咪唑[4,5f][1,10]菲啰啉，研究了这些化合物与 DNA 寡核苷酸 5′-G3(T2AG3)3-3′(HTG21) 的相互作用，采用了 UV-vis 和 circular dichroism (CD) 光谱、凝胶迁移实验、荧光共振能量转移 (FRET) 熔解实验、聚合酶链反应 (PCR) 停止实验及端粒重复扩增协议 (TRAP) 实验。结果显示，两个配合物均能诱导四链体 DNA 的稳定化，但配合物 1 的 G-四链体结合能力优于配合物 2。测试的两个钌配合物都导致了酶端粒酶的抑制，其中配合物 1 的抑制效果显著更好。我们开发了一种新颖的视觉方法，通过我们的钌配合物与 hemin 结合形成 hemin-G-四链体 DNA 酶，以区分 G-四链体 DNA 和双链 DNA。此外，体外细胞毒性研究显示，配合物 1 表现出相当强的抗肿瘤活性，并对癌细胞系具有最大的抑制选择性。
• Mitochondrial Fragmentation Is an Important Cellular Event Induced by Ruthenium(II) Polypyridyl Complexes in Osteosarcoma Cells
  作者：Yanxin Du、Xiaoyan Fu、Hong Li、Bolai Chen、Yuhai Guo、Guoyi Su、Hu Zhang、Feipeng Ning、Yongpeng Lin、Wenjie Mei、Tianfeng Chen

  DOI：10.1002/cmdc.201300379

  日期：2014.4

  A series of ruthenium(II) polypyridyl complexes were synthesized and evaluated for their in vitro anticancer activities. The results showed that ruthenium polypyridyl complexes, especially [Ru(bpy)2(p‐tFPIP)]2+ (2 a; bpy=bipyridine, tFPIP=2‐(2‐trifluoromethane phenyl)imidazole[4,5‐f][1,10]phenanthroline), exhibited novel anticancer activity against human cancer cell lines, but with less toxicity to

  合成了一系列钌（II）聚吡啶基配合物，并对其体外抗癌活性进行了评估。结果表明，钌多吡啶基配合物，特别是[Ru（bpy）2（p- tFPIP）] 2+（2 a ; bpy =联吡啶，tFPIP = 2-（2-三氟甲烷苯基）咪唑[4,5- f ] [ 1,10]菲咯啉对人癌细胞具有新颖的抗癌活性，但对人正常细胞的毒性较小。流式细胞仪和caspase活性分析结果表明，2 a对MG-63骨肉瘤细胞诱导的生长抑制主要是由线粒体介导的细胞凋亡引起的。TUNEL-DAPI共染色检测到的DNA片段化和核浓缩进一步证实了2 a诱导的凋亡细胞死亡。此外，荧光成像显示钌（II）聚吡啶基复合物可以靶向线粒体以诱导线粒体片段化，并伴随着线粒体膜电位的消耗。综上所述，这些发现表明这些钌（II）配合物在癌症治疗中的潜在应用。
• Ruthenium(II) Complexes Coupled by Erianin Via a Flexible Carbon Chain as a Potential Stabilizer of c-myc G-Quadruplex DNA
  作者：Zhixiang Wang、Wentao Liu、Guohu Li、Jiacheng Wang、Bin Zhao、Peishan Huang、Wenjie Mei

  DOI：10.3390/molecules28041529

  日期：——

  Herein, two novel ruthenium(II) complexes coupled by erianin via a flexible carbon chain, [Ru(phen)2(L1-(CH2)4-erianin)](ClO4)2 (L1 = 2-(2-(tri-fluoromethyphenyl))-imidazo [4,5f][1–10]phenanthroline (1) and [Ru(phen)2(L2-(CH2)4-eria)](ClO4)2 (L2 = 2-(4-(tri-fluoromethyphenyl))-imidazo [4,5f][1,10]phenanthroline (2), have been synthesized and investigated as a potential G-quadruplex(G4) DNA stabilizer. Both complexes, especially 2, can bind to c-myc G4 DNA with high affinity by electronic spectra, and the binding constant calculated for 1 and 2 is about 15.1 and 2.05 × 107 M−1, respectively. This was further confirmed by the increase in fluorescence intensity for both complexes. Moreover, the positive band at 265 nm in the CD spectra of c-myc G4 DNA decreased treated with 2, indicating that 2 may bind to c-myc G4 DNA through extern groove binding mode. Furthermore, fluorescence resonance energy transfer (FRET) assay indicated that the melting point of c-myc G4 DNA treated with 1 and 2 increased 15.5 and 16.5 °C, respectively. Finally, molecular docking showed that 1 can bind to c-myc G4 DNA in the extern groove formed by base pairs G7–G9 and G22–A24, and 2 inserts into the small groove of c-myc G4 DNA formed by base pairs T19–A24. In summary, these ruthenium(II) complexes, especially 2, can be developed as potential c-myc G4 DNA stabilizers and will be exploited as potential anticancer agents in the future.

  在此，两种新型钌(II)配合物通过柔性碳链与麦饭石素偶联，即[Ru(phen)2(L1-(CH2)4-麦饭石素)](ClO4)2（L1 = 2-(2-(三氟甲基苯基))-咪唑 [4、1）和[Ru(phen)2(L2-(CH2)4-eria)](ClO4)2（L2 = 2-(4-(三氟甲基苯基))-咪唑并[4,5f][1,10]菲罗啉（2））的合成，并将其作为一种潜在的 G-四链式（G4）DNA 稳定剂进行了研究。从电子能谱上看，这两种复合物，尤其是 2，都能与 c-myc G4 DNA 高亲和力地结合，计算出的 1 和 2 的结合常数分别约为 15.1 和 2.05 × 107 M-1。两种复合物荧光强度的增加进一步证实了这一点。此外，经 2 处理后，c-myc G4 DNA CD 光谱中 265 nm 处的正带减少，这表明 2 可能是通过外沟槽结合模式与 c-myc G4 DNA 结合的。此外，荧光共振能量转移（FRET）检测表明，经 1 和 2 处理的 c-myc G4 DNA 的熔点分别升高了 15.5 ℃ 和 16.5 ℃。最后，分子对接显示，1 能在碱基对 G7-G9 和 G22-A24 形成的外沟槽中与 c-myc G4 DNA 结合，而 2 则插入到碱基对 T19-A24 形成的 c-myc G4 DNA 小沟槽中。总之，这些钌（II）配合物，尤其是 2，可以开发为潜在的 c-myc G4 DNA 稳定剂，并将在未来作为潜在的抗癌剂加以利用。