[chlorido{3-(oxo-κO)-2-(4-fluorophenyl)-chromen-4(1H)-onato-κO}(η⁶-p-cymene)ruthenium(II)] | 1376044-12-0

• 英文名称: [chlorido{3-(oxo-κO)-2-(4-fluorophenyl)-chromen-4(1H)-onato-κO}(η⁶-p-cymene)ruthenium(II)]
• 英文别名: [chlorido{3-(oxo-.κappa.O)-2-(4-fluorophenyl)-chromen-4(1H)-onato-.κappa.O}(η6-pcymene)ruthenium(II)]；[Ru(II)Cl(cym)(C6H4C(O)C(O)C(C6H4-p-F)O)]；Ru(η**(6)-p-cymene)Cl(C9H4O3C6H4F)
• CAS: 1376044-12-0
• 化学式: C₂₅H₂₂ClFO₃Ru
• 分子量: 525.969
• InChiKey: GYWSHQHUYXGVLN-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  7.25
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  39.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  [chlorido{3-(oxo-κO)-2-(4-fluorophenyl)-chromen-4(1H)-onato-κO}(η⁶-p-cymene)ruthenium(II)] 、 乙腈 在 氧气 作用下， 反应 12.0h， 生成 、 、 、
  参考文献：
  名称：

  Photochemical Reactivity of Ru^II(η⁶-p-cymene) Flavonolato Compounds

  摘要：

  Photoactivation is a promising approach for modulating the biological activity of Ru-II compounds. In this work, RuII flavonolato compounds, [Ru(eta(6)-p-cymene)(L)(3-Hfl)]OTf (8; 3-Hfl = monoanion of 3-hydroxyflavone; L = solvent) and [Ru(eta(6)-p-cymene)Cl(3-Hfl-X)] (3a3c; 3-Hfl-X = p-H, -Cl, or -F on the flavonolato phenyl substituent), have been evaluated for photoinduced reactivity within the flavonolato unit upon irradiation with UV (300 nm) or visible (419 nm) light under aerobic conditions. For each compound, irradiation in CH3CN was found to result in the loss of the p-cymene ligand and the formation of products resulting from oxidative ring opening of the flavonolato ligand in a dioxygenase-type reaction. This reaction also results in the release of carbon monoxide. The Ru-II products generated in these reactions are [RuII(solvent)(carboxylato)]+ and [Ru(CO)(solvent)(carboxylato)]+ (carboxylato = O-benzoylsalicylato or benzoato) species, as determined by ESI-MS. The amount of free CO generated depends on the wavelength of irradiation, with 300 nm light giving a higher amount of free CO. Evaluation of the photoinduced reactivity of 8 in DMSO/H2O (10:90) at 300 nm showed similar reactivity to that found in organic solvent, although the reaction occurs more slowly. The products of the photoreactions of 8 and 3a at 419 nm are nontoxic toward human T-lymphocyte (Jurkat) and non-small-cell lung carcinoma (A549) cells. This lack of toxicity versus the starting compounds is likely due to differences in interactions of the [Ru-II(solvent)(carboxylato)]+ and [RuII(CO)(solvent)(carboxylato)]+ species with biomolecules (e.g., serum proteins), thus resulting in reduced bioavailabilty. 1H NMR studies provide evidence that the photoreaction products coordinate to biologically relevant donors such as histidine and 5'-GMP in d(6)-DMSO/D2O (10:90) and exhibit reactivity with these small molecules that is distinctly different from that exhibited by the starting compounds. Overall, the photoreactivity of 8 and 3a3c may represent an approach toward altering the biological chemistry of these compounds.

  DOI：

  10.1021/om5006337
• 作为产物：
  描述：

  2-(4-fluorophenyl)-3-hydroxy-4H-chromen-4-one 、 [RhCl2(p-cymene)]2 在 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 18.0h， 以66%的产率得到[chlorido{3-(oxo-κO)-2-(4-fluorophenyl)-chromen-4(1H)-onato-κO}(η⁶-p-cymene)ruthenium(II)]
  参考文献：
  名称：

  Structure–Activity Relationships of Targeted Ru^II(η⁶-p-Cymene) Anticancer Complexes with Flavonol-Derived Ligands

  摘要：

  Ru-II(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized Ru-II(eta(6)-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multitargeted anticancer agents. To validate this concept, studies on the mode of action of the complexes were conducted which indicated that they form covalent bonds to DNA, have only minor impact on the cell cycle, but inhibit CDK2 and topoisomerase Ha in vitro. The cytotoxic activity was determined in human cancer cell lines, resulting in very low IC50 values as compared to other Ru-II(arene) complexes and showing a structure-activity relationship dependent on the substitution pattern of the flavonol ligand. Furthermore, the inhibition of cell growth correlates well with the topoisomerase inhibitory activity. Compared to the flavonol ligands, the Ru-II(eta(6)-p-cymene) complexes are more potent antiproliferative agents, which can be explained by potential multitargeted properties.

  DOI：

  10.1021/jm301376a

文献信息

• 3-Hydroxyflavones vs. 3-hydroxyquinolinones: structure–activity relationships and stability studies on Ru^II(arene) anticancer complexes with biologically active ligands
  作者：Andrea Kurzwernhart、Wolfgang Kandioller、Éva A. Enyedy、Maria Novak、Michael A. Jakupec、Bernhard K. Keppler、Christian G. Hartinger

  DOI：10.1039/c2dt32206d

  日期：——

  RuII(η6-arene) complexes, especially with bioactive ligands, are considered to be very promising compounds for anticancer drug design. We have shown recently that RuII(η6-p-cymene) complexes with 3-hydroxyflavone ligands exhibit very high in vitro cytotoxic activities correlating with a strong inhibition of topoisomerase IIα. In order to expand our knowledge about the structure–activity relationships and to determine the impact of lipophilicity of the arene ligand and of the hydrolysis rate on anticancer activity, a series of novel 3-hydroxyflavone derived RuII(η6-arene) complexes were synthesised. Furthermore, the impact of the heteroatom in the bioactive ligand backbone was studied by comparing the cytotoxic activity of RuII(η6-p-cymene) complexes of 3-hydroxyquinolinone ligands with that of their 3-hydroxyflavone analogues. To better understand the behaviour of these RuII complexes in aqueous solution, the stability constants and pKa values for complexes and the corresponding ligands were determined. Furthermore, the interaction with the DNA model 5′-GMP and with a series of amino acids was studied in order to identify potential biological target structures.

  RuII(η6-芳烃)配合物，尤其是具有生物活性配体的配合物，被认为是抗癌药物设计中非常有前景的化合物。我们最近已显示，RuII(η6-p-松油烃)配合物与3-羟基黄酮配体表现出非常高的体外细胞毒性活动，这与对拓扑异构酶IIα的强抑制作用相关。为了拓展我们关于结构-活性关系的知识，并确定芳烃配体的亲脂性和水解速率对抗癌活性的影响，我们合成了一系列新型的以3-羟基黄酮为基础的RuII(η6-芳烃)配合物。此外，通过比较RuII(η6-p-松油烃)配合物与3-羟基喹啉酮配体和其3-羟基黄酮类似物的细胞毒性活性，研究了生物活性配体骨架中杂原子的影响。为了更好地理解这些RuII配合物在水溶液中的行为，确定了配合物及其相应配体的稳定性常数和pKa值。此外，还研究了与DNA模型5′-GMP和一系列氨基酸的相互作用，以识别潜在的生物靶标结构。
• Targeting the DNA-topoisomerase complex in a double-strike approach with a topoisomerase inhibiting moiety and covalent DNA binder
  作者：Andrea Kurzwernhart、Wolfgang Kandioller、Caroline Bartel、Simone Bächler、Robert Trondl、Gerhard Mühlgassner、Michael A. Jakupec、Vladimir B. Arion、Doris Marko、Bernhard K. Keppler、Christian G. Hartinger

  DOI：10.1039/c2cc31040f

  日期：——

  RuII(arene)–flavonoids with high in vitro antitumour activity were synthesised. These compounds are capable of inhibiting human topoisomerase IIα and binding covalently to DNA.

  合成了具有高体外抗肿瘤活性的 RuII（芴）类黄酮。这些化合物能够抑制人类拓扑异构酶 IIα 并与 DNA 共价结合。