DICHLOROBIS(CYCLOALKYLAMINE)PLATINUM(II) COMPLEXES STRUCTURE-ACTIVITYRELATIONSHIP ON THE HUMAN MDA-MB-231 BREAST-CANCER CELL-LINE

The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes wi th cis and trans cycloalkylamine ligands [cis-PtCl2(C3H5NH2)2 to cis-P tCl2(C8H15NH2)2 (3-8) and trans-PtCl2-(C7H13NH2)2 (9) and trans-PtCl2( C8H15NH2)2 (10)] are described. The distinction between cis and trans isomers was achieved by H-1-NMR spectroscopy. The antitumor activity w as determined on the cell proliferation of the human MDA-MB-231 breast cancer cell line during long-term drug exposure. The complexes with s mall cycloalkylamine ligands (3-6) were inferior, those with large cyc loalkylamine ligands were comparable (7) or superior (8) to cisplatin. Surprisingly, the cis/trans isomers 7/9 and 8/10 were equally active. All cycloalkylamine ligands were inactive. IR-spectroscopic studies s howed that the size of the cycloalkylamine ring does not lead to signi ficant differences in the Pt-Cl binding strength. Therefore it is assu med that the markedly stronger antitumor activity of the higher homolo gues, 7-10, is not the result of a faster reaction with bionucleophils such as DNA. A possible explanation of the high activity of 7-10 is t he strong lipophilicity of the complexes. This assumption was confirme d by toxicity tests against confluent cultures.