Dichlorobis(cycloalkylamine)platinum(II) complexes structure activity relationship on the human MDA-MB-231 breast cancer cell line |
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Authors: | J. Kritzenberger G. Bernhardt R. Gust P. Pistor H. Schönenberger H. Yersin |
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Affiliation: | (1) Institut für Physikalische und Theoretische Chemie, Universität Regensburg, D-W-8400 Regensburg, Federal Republic of Germany;(2) Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg, D-W-8400 Regensburg, Federal Republic of Germany;(3) Present address: Department of Chemistry, University of California, 94720 Berkeley, California, U.S.A. |
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Abstract: | Summary The syntheses of dichlorobis(cycloalkylamine)platinum(II) complexes withcis andtrans cycloalkylamine ligands [cis-PtCl2(C3H5NH2)2 tocis-PtCl2(C8H15NH2)2 (3–8) andtrans-PtCl2(C7H13NH2)2 (9) andtrans-PtCl2(C8H15NH2)2 (10)] are described. The distinction betweencis andtrans isomers was achieved by1H-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, thecis/trans isomers7/9 and8/10 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 bionucleophils such as DNA. A possible explanation of the high activity of7–10 is the strong lipophilicity of the complexes. This assumption was confirmed by toxicity tests against confluent cultures.In memory of Professor Dr. Günter Gliemann, late director of the Institut für Physikalische und Theoretische Chemie, Universität Regensburg. |
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Keywords: | cis- andtrans-Dichlorobis(cycloalkylamine)platinum(II) complexes Antitumor activity MDA-MB-231 Breast cancer cell line |
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