Synthesis and in vitro antitumor potency of (cyclohexane-1,2-diamine) platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking ligand

In order to develop platinum complexes with selective activity in primary and secondary bonemalignancies and with the aim to optimize antitumor activity, platinum(II) complexes withaminotris(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 diamineligands, 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 incomplexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in theorder 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 vitropotency than the corresponding cis isomer (I), with the trans-R,R isomer (3) being the most active in thisseries. In comparison to the analogous (cyclohexane-1,2-diamine) platinum(II) complexes withbis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be1.5 - 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands(acetato versus phosphonato).