铂(Ⅳ)类配合物的合成及其抗肿瘤活性

Synthesis and antineoplastic activity evaluations of platinum(Ⅳ)complexes

目的寻求高效低毒的新一代铂类抗肿瘤药物。方法以六氯合铂 (Ⅳ )酸钾 (K2 PtCl6)为原料 ,设计合成了一系列顺铂 (cisplatin)类似物 ,将其依次氧化、酰化 ,合成了 11个新型铂 (Ⅳ )类配合物 ,结构通式为 :PtCl2 (OR1) 2 (NH2 R) 2 。并以溴化乙锭 (Etd)为荧光探针 ,通过配合物与DNA相互作用而引起体系的荧光变化 ,测定最大荧光淬灭百分率 (Rm) ,计算结合常数Km ,由此推测配合物抗癌活性。结果所合成铂 (Ⅳ )配合物的化学结构由元素分析和光谱分析所证实 ,其中 7个化合物 (6c～ 6e ,7c～7f)尚未见文献报道。试验测得受试配合物Rm值和Km计算值均较顺铂低 ,其活性顺序为 :顺铂 >6a >6c>6d。结论铂 (Ⅳ )配合物是一类具有重要研究价值和开发前景的抗肿瘤剂。

Aim To find the new generation of high potential,low toxic and broad spectrum Pt based anticancer drugs.Method A series of the novel platinum(Ⅳ)complexes was designed and synthesized.The general formula of these compounds was PtCl 2(OR 1) 2(NH 2R) 2,where R meant hydrogen or alkyl and alcyl groups and R 1 meant hydrogen or acyl groups.The antineoplastic activity of the platinum(Ⅳ)complexes was performed by evaluating the ability of binding to DNA against a fluorescent probe of Ethidium bromide(EB).The binding constants( K m)and maximum ratios of fluorescent extinction were used to judge the results.Result The structures of all the compounds had been elucidated by IR,MS spectra and elementary analysis.The ratio of fluorescent extinction of the tested platinum(Ⅳ)complexes were detected and found to be lower than that of the reference drug of cisplatin,thus the corresponding calculated binding constants( K m)of Pt(Ⅳ)complex with DNA were in the following reducing sequence:cisplatin>6a>6c>6d.Conclusion The platinum(Ⅳ)complexes,as new leads of antineoplastic agents,are promising and worthy of being further studied.