Synthesis, crystal structure and biological activities of a novel amidrazone derivative and its copper(II) complex — A potential antitumor drug

Abstract

A new linear amidrazone derivative, 6-acetyl-cyclohex-3-enecarboxylic acid [1-pyridin-2-yl-1-(pyridyn-2-yloamin)meth-(Z)-ylidene] hydrazide, H2L (2) and its Cu(II) complex, [Cu2L2]·4H2O (3) were synthesized and characterized by elemental analysis, IR and 1H NMR spectroscopy and cyclic voltammetry. Compound 2 was synthesized in the equimolar reaction of N3-substituted amidrazone with cis-1,2,3,6-tetrahydrophthalic anhydride. The Cu complex of 2 was obtained in the reaction with copper(II) acetate. The molecular structures of 2 and 3 were determined by X-ray crystallography. The parent ligand exists in its amide-hydrazone form in the solid state. The central amidrazone moiety has a Z configuration with respect to the double CN bond. Coordination to the metal center promotes Z/E isomerization of the hydrazone group of the ligand. Compound 3 is a dinuclear four-coordinated Cu(II) complex with the amidrazone ligand behaving as a tetradentate double deprotonated chelating one. Several biological activities of 2 and 3 were examined in vitro; they were: antimicrobial properties against selected bacterial and fungal strains, suppression of phytohemagglutinin A (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMC) and their effects on tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) production. The cytotoxic activity of Cu(II) complex was determined with respect to the four carcinoma cell lines (SW 984, CX-1, L-1210, A-431). The studied complex exhibited significant cytotoxic effects (particularly against CX-1 colon carcinoma), comparable to those reported for cisplatin. Both compounds have shown a relatively low antibacterial activity and were devoid of antifungal properties.