Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate.
Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate.
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DOI：
10.1016/j.jinorgbio.2015.02.002
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发表时间：
2015-05
影响因子：
3.9
通讯作者：
Weiping Liu;Jing Jiang;Yongping Xu;Shuqian Hou;L. Sun;Qingsong Ye;L. Lou
中科院分区：
文献类型：
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作者：
Weiping Liu;Jing Jiang;Yongping Xu;Shuqian Hou;L. Sun;Qingsong Ye;L. Lou
合成了4个新的含二氯乙酸环丁烷-1，1-二羧酸酯结构的二胺铂配合物，通过元素分析和电喷雾质谱对其结构进行了表征（正离子模式下的电喷雾电离质谱法），FT-IR，1H-和13 C-NMR，体外抗人肺癌细胞株（A549）和卵巢癌细胞株（SK-OV-3、SK-OV-3/DDP）活性。本研究中使用的二胺属于六种临床批准的铂类药物的载体。在所合成的配合物中，配合物2，cis-[Pt（II）（1 R，2 R-diaminocyclohexane）·（3-dichoroacetoxylcyclobutane-1，1-dicarboxylate）]在水溶性和与顺铂完全没有交叉耐药性方面是最有前途的。因此，选择络合物2用于二氯乙酸盐释放测试。实验结果表明，在生理条件下，二氯乙酸酯可通过酯键的水解从络合物2中有效释放出来，酯键将二氯乙酸酯和铂药效团连接在一起。我们的研究支持进一步评估这种复杂的候选药物。
Four new diam(m)ine platinum complexes containing the dichloroacetate moiety in 3-dichoroacetoxylcyclobutane-1,1-dicarboxylate as the leaving group were synthesized, characterized by elemental analysis as well as by ESI+-MS (electrospray ionization mass spectrometry in positive mode), FT-IR,1H- and13C-NMR, and evaluated for theirin vitroanticancer activity against human lung cancer cell line (A549) and ovarian cancer cell lines (SK-OV-3, SK-OV-3/DDP). Diam(m)ines used in the present study belong to the carriers of six clinically approved platinum drugs. Among the complexes synthesized, complex2,cis-[Pt(II)(1R,2R-diaminocyclohexane)·(3-dichoroacetoxylcyclobutane-1,1-dicarboxylate)] is the most promising in terms of water solubility and potential of being totally devoid of cross-drug resistance with cisplatin. Therefore, complex2was selected for the dichloroacetate release test. The test shows dichloroacetate can be efficiently released from complex2under physiological conditions via the hydrolysis of an ester bond bridging the dichloroacetate moiety and platinum pharmacophores together. Our study supports the further evaluation of this complex as a drug candidate.