Anti-cancer and anti-angiogenic activities of some synthetic Ni(II) thiosemicarbazone complexes

Abstract

Synthesis and X-ray structural characterization of three Ni(II) complexes of thiosemicarbazone ligand [Ni(L1)2] (1), [Ni(L2)]2 (2) and [Ni(L3)2] (3) [L1 = 2-ethoxybenzaldehyde-N(4)-diethyl-3-thiosemicarbazone, L2 = o-vanillin-N(4)-diethyl-3-thiosemicarbazone and L3 = 2-benzoylpyridine-N(4)-diethyl-3-thiosemicarbazone] are reported. From the structural characterization data, the metal centers in 1 and 2 are found to have distorted square planar geometries but in 3, the Ni(II) center adopts distorted octahedral geometry. The metal complexes (1, 2 and 3) show anti-cancer and anti-angiogenic activities. The complexes act in dual mode by both inhibiting the growth of the cancer cells directly through inducing intracellular Reactive Oxygen Species (ROS) level and inhibiting the growth of blood vessels which can indirectly retard and inhibit tumor growth and progression. Angiogenesis assay performed in in vivo Chorio-Allantoic Membrane (CAM) assay indicated that the complexes significantly inhibited the blood capillary growth within 24 h. The anti-angiogenic effect was observed to be effective against all the key cells involved in angiogenesis namely endothelial cell, fibroblast and smooth muscle cell of the blood vessel as observed in aortic arch assay where the complexes exhibited inhibitory effect on aortic capillary sprouting.