In:
Bioinorganic Chemistry and Applications, Hindawi Limited, Vol. 3, No. 3-4 ( 2005), p. 179-190
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).
Type of Medium:
Online Resource
ISSN:
1565-3633
DOI:
10.1155/BCA.2005.179
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2005
detail.hit.zdb_id:
2213020-2
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