In vitro and in vivo studies of neutral cyclometallated complexes against murine leukaemias

Cyclometallated mu-halogeno dimers derived from nitrogen donor ligands (1-phenylpyrazoles, 2-phenylpyridine, and 1-(2'-pyridyl)indole) were treated with unidentate nitrogen and phosphorus donor ligands to give a series of neutral monomeric palladium(II) and platinum(II) complexes. An initial prescreen of the complexes against the mouse lymphoid leukaemia cell line L1210 indicated that the complexes exhibited growth inhibitory activity over a relatively wide concentration range. Two factors that gave rise to increased activity were steric hindrance about the metal centre resulting from hindered ligands such as 2,6-dimethylpyridine, or the presence of a phosphorus donor ligand. Little correlation between palladium and platinum complexes was noted. Four complexes were selected for further in vivo study and, while none of the palladium complexes showed more than marginal activity against P388 leukaemia at doses below toxic levels, one platinum complex with a hindered metal centre did display significant antitumour activity against this model.