Dichlorobis(cycloalkylamine)platinum(II) complexes. Structure activity relationship on the human MDA-MB-231 breast cancer cell line

The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes with cis and trans cycloalkylamine ligands [cis-PtCl2(C3H5NH2)2 to cis-PtCl2(C8H15NH2)2 and trans-PtCl2(C7H13NH2)2 and trans-PtCl2(C8H15NH2)2 are described. The distinction between cis and trans isomers was achieved by 1H-NMR spectroscopy. The antitumor activity was detd. on the cell proliferation of the human MDA-MB-231 breast cancer cell line during long-term drug exposure. The complexes with small cycloalkylamine ligands were inferior, those with large cycloalkylamine ligands were comparable or superior to cisplatin. All cycloalkylamine ligands were inactive. IR spectroscopic studies showed that the size of the cycloalkylamine ring does not lead to significant differences in the Pt-Cl binding strength. Therefore it is assumed that the markedly stronger antitumor activity of the higher homologs is not the result of a faster reaction with bionucleophiles such as DNA. A possible explanation of the high activity of some of the isomers is the strong lipophilicity of the complexes. This assumption was confirmed by toxicity tests against confluent cultures