Synthesis, Solution Chemistry, X-ray Structure and Biological Activity of Novel Pyridoxal Thiosemicarbazone Derivatives

Abstract

Abstract Novel ligands were obtained by condensation of pyridoxal with thiosemicarbazides substituted with alkyl and aryl moieties on the aminic and/or hydrazinic nitrogen. The spectrophotometric characteristics of the various species are reported. The X-ray structure of two different dimethylthiosemicarbazones of pyridoxal — pyridoxal N1,N2-dimethylthiosemicarbazone monohydrate and pyridoxal N1,N1-dimethylthiosemicarbazone monohydrate — was determined. The change of methyl group position determines in the solid state strong differences which affect the ligand behavior of these compounds. In the first ligand, characterized by X-ray diffraction, the pyridoxal ring is in a zwitterion form, with the phenolic oxygen and the sulfur atoms in trans position to the iminic N atom. The second compound, with both methyl groups on the aminic nitrogen, shows the donor atoms SNO on the same side, making it potentially suitable for coordination to the metal. Biological studies have involved both inhibition of cell proliferation and apoptosis tests on human leukemia cell lines U937. Both ligands inhibited cell growth, but neither of them induced apoptosis. On the basis of the pKa values, the second ligand is more easily dissociable and this allows us to predict the formation of neutral complexes with it.