In order to develop platinum complexes with selective activity in primary and secondary bone malignancies and with the aim to optimize antitumor activity, platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking (osteotropic) ligand have been synthesized, characterized and tested in the cisplatin-sensitive ovarian carcinoma cell line CH1. As non-leaving diamine ligands, which are decisive for the cellular processing of DNA adducts, cis-R,S-cyclohexane-1,2-diamine, trans-S,S-cyclohexane-1,2-diamine and trans-R,R-cyclohexane-1,2-diamine have been used, resulting in complexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in the order 3 > 2 > 1 which is in accord with structure-activity relationships with other (cyclohexane-1,2- diamine)platinum(II) and platinum(IV) complexes: Both trans complexes (2 and 3) display a higher in vitro potency than the corresponding cis isomer (I), with the trans-R,R isomer (3) being the most active in this series. In comparison to the analogous (cyclohexane-1,2-diamine)platinum(II) complexes with bis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be 1.5 - 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands (acetato versus phosphonato).

中文翻译：

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（环己烷-1,2-二胺）铂（II）复合物与氨基三（亚甲基膦酸）作为寻骨配体的合成和体外抗肿瘤效力。

为了开发在原发性和继发性骨恶性肿瘤中具有选择性活性的铂配合物并以优化抗肿瘤活性为目的，已经合成、表征和测试了以氨基三（亚甲基膦酸）为骨寻求（骨性）配体的铂 (II) 配合物在顺铂敏感的卵巢癌细胞系 CH1 中。作为非游离二胺配体，对 DNA 加合物的细胞加工具有决定性作用，顺式-R,S-环己烷-1,2-二胺、反式-S,S-环己烷-1,2-二胺和反式-R，已使用 R-环己烷-1,2-二胺，分别生成配合物 1、2 和 3。所研究配合物的细胞毒性以 3 > 2 > 1 的顺序降低，这与其他（环己烷-1,2-二胺）铂（II）和铂（IV）配合物的构效关系一致：两种反式复合物（2 和 3）都显示出比相应的顺式异构体 (I) 更高的体外效力，其中反式 R,R 异构体 (3) 是该系列中最活跃的。与类似的（环己烷-1,2-二胺）铂（II）复合物与双（膦酰基甲基）氨基乙酸作为骨载体配体相比，发现1-3的细胞毒性高1.5-2倍，这是可以解释的通过膦酸配体的不同配位模式（乙酸根与膦酸根）。