DNA靶向手性钌(Ⅱ)配合物的合成、表征及其抗肿瘤作用

Synthesis,characterization and inhibitory activity against tumor cells of chiral ruthenium(Ⅱ) complexes targeted to DNA

目的设计合成2个手性钌(Ⅱ)多吡啶配合物Λ-[Ru(bpy)2(p-NPIP)](PF6)2.2H2O(1)和Λ-[Ru(bpy)2(p-tFPIP)](PF6)2.2H2O(2),评价其体外抗肿瘤活性,并对配合物2与DNA分子的识别机制及其光裂解作用进行初步探讨。方法采用MTT方法评价手性钌(Ⅱ)配合物1和2对肿瘤细胞生长的抑制,并采用电子吸收光谱、荧光光谱和黏度试验等方法研究手性钌配合物2与DNA的分子识别机制;采用凝胶电泳试验评价配合物2对DNA分子的光裂解作用。结果手性钌(Ⅱ)配合物2能够抑制肿瘤细胞的生长,特别是对HO8910PM细胞生长的抑制率IC50=47.8μmol.L-1,与同等条件下顺铂的抗肿瘤活性相当;研究结果表明插入配体上取代基的电子效应对其抗肿瘤活性有较大影响;光谱学试验证明钌多吡啶配合物1和2通过插入方式与DNA结合(Kb=2.86×105 L.mol-1)。结论手性钌(Ⅱ)多吡啶配合物具有一定的抗肿瘤活性,其抗肿瘤活性与钌(Ⅱ)配合物的分子结构及其与DNA分子契合能力相关。

Objective To synthesize and characterize two chiral ruthenium（Ⅱ） complexes Λ-[Ru（bpy）2（p-NPIP）]（PF6）2·2H2O（1） and Λ-[Ru（bpy）2（p-tFPIP）]（PF6）2·2H2O（2） by ES-MS,1H-NMR and CD spectra,and investigate the antitumor activity of both complexes and its interaction with DNA.Methods The antitumor activity of the two complexes against tumor cells were evaluated by MTT methods,and the interaction of chiral ruthenium（Ⅱ） complex 2 with calf thymus DNA has been investigated by electronic absorption spectra and fluorescent spectra,as well as viscosity measurements.Results The results show that complex 2 exhibits excellent inhibitory activity against HO8910PM cell with IC50=47.8 μmol·L-1,which is comparable to that of cis-platinum at the same conditions,and the chiral ruthenium complex binds to DNA through intercalation mode with binding constant measured with 2.86×10^5 mol·L^-1Conclusion The chiral ruthenium（Ⅱ） complexes exhibit promising anti-tumor activity against varied tumor cells,which involves the binding properties of ruthenium（Ⅱ） complexes with DNA molecules.