Cisplatin, cis-diammineplatinum(II) dichloride, is a
metal complex used in clinical practice for the treatment of
cancer. Despite its great efficacy, it causes adverse reactions and most patients develop a resistance to
cisplatin. To overcome these issues, a multi-
drug therapy was introduced as a modern approach to exploit the
drug synergy. A synergistic effect had been previously found when testing binary combinations of
cisplatin and three
copper complexes in vitro, namely, Cu(phen)(OH2)2(OClO3)2, [
Cu(phen)2(OH2)](ClO4)2 and [
Cu(phen)2(H2dit)](ClO4)2,(phen=1,10-
phenanthroline, H2dit=
imidazolidine-2-
thione), against the human acute T-lymphoblastic leukaemia cell line (CCRF-CEM). In this work [
Cu(phen)2(OH2)](ClO4)2 was also tested in combination with
cisplatin against
cisplatin-resistant sublines of CCRF-CEM (CCRF-CEM-res) and ovarian (A2780-res)
cancer cell lines. The tested combinations show a synergistic effect against both the types of resistant cells. The possibility that this effect was caused by the formation of new adducts was considered and mass spectra of solutions containing
cisplatin and one of the three
copper complexes at a time were measured using electrospray ionisation at atmospheric-pressure mass spectrometry (ESI-MS). A mixed complex was detected and its stoichiometry was assessed on the basis of the isotopic pattern and the results of tandem mass spectrometry experiments. The formed complex was found to be [Cu(phen)(
OH)μ-(Cl)2Pt(NH3)(H2O)](+).