Synthesis, spectroscopy, X-ray analysis and in vitro antiproliferative effect of ferrocenylmethylene-hydrazinylpyridazin-3(2H)-ones and related ferroceno[d]pyridazin-1(2H)-ones

Synthesis, structure determination and in vitro antiproliferative assay of a series of novel ferrocenenyl hydrazones containing 4-halopyridazin-3(2H)-one fragment(s) and three representative N-aryl-substituted (Sp)-ferroceno[d]pyridazinones are presented. The model compounds can be considered as different assemblies of the potential binding sites capable of establishing interactions including hydrogen bonds and π-π interactions with the relevant residues of biomolecules. Their in vitro antiproliferative effect was investigated against four tumorous cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. Our data indicate that bis-hydrazone of 1,1′-diformylferrocene carrying N-benzyl substituents and a chloropyridazinyl-substituted ferroceno[d]pyridazinone display significant activity on each cell lines investigated. The efficiency of the latter drug candidate and one N-benzyl mono-hydrazone on A2870 cell line is comparable to that of cisplatin. The constitution and relative configuration of the model compounds were established by 1H, 13C and 15N NMR methods. The structures of a mono- and bis-ferrocenylhydrazone containing 4-bromopyridazinone unit(s) were confirmed by single crystal X-ray diffraction.