Abstract：
Two copper(II) complexes containing diplacone (H4dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu3(bphen)3(Hdipl)2]⋅2H2O (1) and {[Cu(phen)(H2dipl)2]⋅1.25H2O}n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC50 ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC50 ≈ 2 μM) and osteosarcoma (HOS, with IC50 ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes.
摘要：
两种含迪拉酮（H4dipl）的铜（II）配合物，一种天然存在的C-香叶化黄烷酮衍生物，制备并表征了与红菲咯啉（bphen）或1,10-菲咯啉（phen）组合的组合物[Cu3（bphen）3（Hdipl）2]·2H2O（1）和{[Cu（phen）（H2dipl）2]·1.25H2O}n（2）。与Diplacone相比，该复合物增强了对A2780和A2780R人卵巢癌细胞的体外细胞毒性（IC50≈0.4-1.2μM），人肺癌（A549，IC50≈2μM）和骨肉瘤（HOS，IC50≈3μM)。使用流式细胞术研究复合物在A2780细胞中的细胞效应，涵盖有关细胞周期停滞的研究，诱导细胞死亡和自噬以及诱导细胞内ROS/超氧化物产生。这些结果揭示了以G2/M细胞周期停滞为特征的可能作用机制。对人类内皮细胞的研究表明，复合物1和2以及它们的亲本化合物diplacone，在抑制NF-κB方面具有抗炎活性。至于对PPARα和/或PPARγ的影响，复合物2降低了白细胞粘附分子VCAM-1和E-选择素的表达，表明其具有双重抗炎能力。通过在含水介质中的质谱研究，证明了各种各样的含铜配位物种和游离的狄拉克酮配体，这可能是复合物多峰效应的原因。
