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

• Four new complexes bearing a cationic ligand were synthesized.
• Addition of N,N-polypyridyl ligands enhance the cytotoxicity of the compounds.
• Generally, the compounds are more cytotoxic against PC-3.
• The complex with phenanthroline has IC50 value of 3.2 μΜ against PC-3.
• The complexes can inhibit topo I through the binding to DNA and the enzyme.

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 IC50 value of 3.2 μΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.

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