Novel Pt(II) anticancer agents and their Pd(II) analogues: syntheses, crystal structures, reactions with nucleobases and cytotoxicities

Five novel cisplatin analogues as well as their equivalent palladium compou nds were prepared using the chelating ligands 2-(2-pyridyl)benzimidazole (p bi), 2-(2-pyridyl)-5,6-dimethylbenzimidazole (pdbi), 2-(2-pyrazyl)-5,6-dime thylbenzimidazole (padbi), bis(pyridine-2-yl)methane (bpm), and (2,2 ' -dip yridyl)propylamine (dppa). The reactions of [Pt(dppa)(H2O)(2)](2+) with the model nucleobase 3-methylpyridone (3-MeP) and [Pd(bpm)(H2O)(2)](2+) with t he model nucleobase 1-methylthymine (1-MeT) were studied. The products were characterised by X-ray structure analysis. The resulting compound bis(mu - 3-methyl-2-pyridone-N3-O4)bis [((2,2 ' -dipyridyl)propylamine)platinum(II)] .tetrafluoroborate (7) shows a head-to-tail orientation concerning the bri dging model nucleobases whereas bis(mu -1-methylthyminato-N3-O4)bis [(bis(p yridine-2-yl)methan)palladium(II) perchlorate. Dihydrate (8) contains the t wo model nucleobases in a head-to-head orientation. In addition to the X-ra y structure analyses of [dichloro(2-(2-pyridyl)benzimidazole)palladium(II)] (1), [dichloro (2-(2-pyridyl)-5, 6-dimethylbenzimidazole)palladium(II)1 DM F (2) and [dichloro(2-(2-pyrazyl)-5, 6-dimethylbenzimidazole)palladium(II)] .DMF (3), the antitumour activities of the corresponding platinum compounds were compared to the activity of cisplatin in one fibroblast and eight bra in tumour cell lines. (C) 2001 Published by Elsevier Science B.V.