Dichlorobis(cycloalkylamine)platinum(II) Complexes. Structure Activity Relationship on the Human MDA-MB-231 Breast Cancer Cell Line

Article abstract of DOI:10.1007/BF00819526

The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes with cis and trans cycloalkylamine ligands are described.The distinction between cis and trans isomers was achieved by (1)H-NMR spectroscopy.The antitumor activity was determined 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 (3-6) were inferior, those with large cycloalkylamine 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 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 homologues, 7-10, is not the result of a faster reaction with binucleophiles such as DNA.A possible explanation of the high activity of 7-10 is the strong lipophilicity of the complexes.This assumption was confirmed by toxicity tests against confluent cultures. Key words: cis- and trans-Dichlorobis(cycloalkylamine)platinum(II) complexes; antitumor activity; MDA-MB-231 breast cancer cell line.