title: Synthesis and in vitro antitumor potency of (cyclohexane-1,2-diamine)platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking ligand.
abstract: 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).
authors: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, Vienna A-1090, Austria. markus.galanski@univie.ac.at
authors: Markus
authors: M
authors: Galanski
authors: Susanna
authors: S
authors: Slaby
authors: Michael A
authors: MA
authors: Jakupec
authors: Bernhard K
authors: BK
authors: Keppler