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新型含细胞周期蛋白依赖性激酶抑制剂的铂（II）和钯（II）配合物：合成、表征及抗肿瘤活性

Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: synthesis, characterization and antitumour activity.

作者信息

Szucová Lucie, Trávnícek Zdenek, Zatloukal Marek, Popa Igor

机构信息

Department of Inorganic Chemistry, Palacký University, Krízkovského 10, CZ-771 47 Olomouc, Czech Republic.

出版信息

Bioorg Med Chem. 2006 Jan 15;14(2):479-91. doi: 10.1016/j.bmc.2005.08.033. Epub 2005 Sep 28.

DOI:10.1016/j.bmc.2005.08.033
PMID:16198575
Abstract

The Pt(II) and Pd(II) complexes of the types cis-[Pt(L(1))(2)Cl(2)].H(2)O (1), cis-[Pt(L(2))(2)Cl(2)].3H(2)O (2), trans-[Pd(L(1))(2)Cl(2)].H(2)O (3), trans-[Pd(L(2))(2)Cl(2)].H(2)O (4), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) (L(1)-L(4)=cyclin-dependent kinase inhibitors derived from 6-benzylamino-9-isopropylpurine) have been prepared and characterized. The complexes have been studied by elemental analyses, conductivity measurements, ES+ MS, FT-IR, (1)H, (13)C and (195)Pt NMR spectra, differential scanning calorimetry and thermogravimetric analysis. The molecular structures of L(1), trans-[Pd(L(3))(2)Cl(2)].2DMF (5) and trans-[Pd(L(4))(2)Cl(2)].2DMF (6) have been determined by single crystal X-ray analysis. The complexes have been tested in vitro due to their presumable anticancer activity against the following human cancer cell lines: K-562, MCF7, G-361 and HOS. Satisfying results were obtained for the complex 1 with IC(50) values of 6 microM acquired against G-361 as well as against HOS cell lines. The lowest values of IC(50) were achieved for the complexes 3 and 4 against MCF 7 cell line with IC(50) 3 microM(for 3) and also 3 microM (for 4).

摘要

已制备并表征了顺式-[Pt(L(1))(2)Cl(2)].H(2)O (1)、顺式-[Pt(L(2))(2)Cl(2)].3H(2)O (2)、反式-[Pd(L(1))(2)Cl(2)].H(2)O (3)、反式-[Pd(L(2))(2)Cl(2)].H(2)O (4)、反式-[Pd(L(3))(2)Cl(2)].2DMF (5) 和反式-[Pd(L(4))(2)Cl(2)].2DMF (6) 类型的Pt(II)和Pd(II)配合物（L(1)-L(4)=源自6-苄基氨基-9-异丙基嘌呤的细胞周期蛋白依赖性激酶抑制剂）。通过元素分析、电导率测量、ES+ MS、FT-IR、(1)H、(13)C和(195)Pt NMR光谱、差示扫描量热法和热重分析对这些配合物进行了研究。通过单晶X射线分析确定了L(1)、反式-[Pd(L(3))(2)Cl(2)].2DMF (5) 和反式-[Pd(L(4))(2)Cl(2)].2DMF (6) 的分子结构。由于这些配合物对以下人类癌细胞系可能具有抗癌活性，因此对其进行了体外测试：K-562、MCF7、G-361和HOS。配合物1在针对G-361以及HOS细胞系时获得了IC(50)值为6 microM的令人满意的结果。配合物3和4针对MCF 7细胞系达到了最低的IC(50)值，IC(50)为3 microM（对于3）以及3 microM（对于4）。

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