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 (S-p)-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 pi-pi 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 H-1, C-13 and N-15 NMR methods. The structures of a mono-and bis-ferrocenylhydrazone containing 4-bromopyridazinone unit(s) were confirmed by single crystal X-ray diffraction. (C) 2013 Elsevier B.V. All rights reserved.