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 compounds were prepared using the chelating ligands 2-(2-pyridyl)benzimidazole (pbi), 2-(2-pyridyl)-5,6-dimethylbenzimidazole (pdbi), 2-(2-pyrazyl)-5,6-dimethylbenzimidazole (padbi), bis(pyridine-2-yl)methane (bpm), and (2,2 ' -dipyridyl)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 the 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 bridging model nucleobases whereas bis(mu -1-methylthyminato-N3-O4)bis [(bis(pyridine-2-yl)methan)palladium(II) perchlorate. Dihydrate (8) contains the two model nucleobases in a head-to-head orientation. In addition to the X-ray structure analyses of [dichloro(2-(2-pyridyl)benzimidazole)palladium(II)] (1), [dichloro (2-(2-pyridyl)-5, 6-dimethylbenzimidazole)palladium(II)1 DMF (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 brain tumour cell lines. (C) 2001 Published by Elsevier Science B.V.