Copper complexes with phosphonium containing hydrazone ligand: topoisomerase inhibition and cytotoxicity study.

Abstract Four new copper(II) complexes containing phosphonium substituted hydrazone (L) with the formulations [CuL]Cl( 3 ), [Cu(phen)L]Cl( 4 ), [Cu(bpy)L]Cl( 5 ), [Cu(dbpy)L]Cl( 6 ), (where L = doubly deprotonated hydrazone; phen = 1,10′-phenanthroline; bpy = 2,2′-bipyridine; dbpy = 5,5′-dimethyl-2,2′-bipyridine) have been synthesized. The compounds were characterized by elemental analysis, spectroscopic methods and in the case of crystalline products by X-ray crystallography. The cytotoxicity and topoisomerase I (topo I) inhibition activities of these compounds were studied. It is noteworthy that the addition of N,N-ligands to the copper(II) complex lead to the enhancement in the cytotoxicity of the compounds, especially against human prostate adenocarcinoma cell line (PC-3). Complex 4 exhibits the highest activity against PC-3 with the IC 50 value of 3.2 μΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.