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

Abstract

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)(H 2O) 2] 2+ with the model nucleobase 3-methylpyridone (3-MeP) and [Pd(bpm)(H 2O) 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(μ-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 nucleo-bases whereas bis(μ-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)]·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.