Three new asymmetric platinum(II) complexes comprising an isopropylamine ligand trans to an azole ligand were synthesized and fully characterized by 1 H NMR, 195 Pt NMR, IR and elemental analysis. In addition the X-ray crystal structure of all three complexes was determined. The reaction kinetics of the complexes with DNA model base guanosine-5 0 -monophosphate (GMP) was studied, revealing reaction kinetics comparable to cisplatin. To gain insight in the complexes as potential antitumor agents, cytotoxicity assays were performed on a variety of human tumor cell lines. These assays showed the complexes all to possess cytotoxicity profiles comparable to cisplatin. Furthermore, the complexes largely retain their activity in a human ovarian carcinoma cell line resistant to cisplatin, A2780R, compared to the cisplatin sensitive parent cell line A2780. These results are of fundamental importance, illustrating how platinum complexes of trans geometry can show improved activity compared to cisplatin in both cisplatin sensitive and cisplatin resistant cell lines.

New asymmetric trans-platinum(II) complexes, composed of an isopropylamine, an azole and two carboxylate leaving groups, are presented. The crystal and molecular structures of one of the complexes has been determined and the cytotoxicity and reactivity with 5 -guanosine monophosphate is reported. The complexes show a reduced reactivity, but no decrease in cytotoxic activity compared to their chloro-counterparts. Furthermore the complexes largely overcome cisplatin resistance, they therefore present an interesting class of antitumour active trans-platinum complexes.

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Asymmetric cis-platinum(II) complexes with isopropylamine and two different azole ligands were synthesized and characterized with different techniques. In addition, for one of the complexes the X-ray structure was determined. Cytotoxicity tests using several human tumor cell lines, including the cisplatin-sensitive cell line A2780 and its cisplatin-resistant analogue. These results were compared with the results obtained for the trans isomers of the presented complexes and a relation between the structure and the activity was established. It was found that complexes with cis geometry are less active than their trans analogues, in particular in the resistant cell line A2780R. However, complex 1 can overcome cisplatin resistance to a certain extent. In the interaction with GMP, the asymmetric cis-Pt(II) complexes react with similar rates as their trans analogues and they behave as bifunctional species.

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