Ternary and binary copper(II) complexes: synthesis, characterization, ROS-inductive, proteasome inhibitory, and anticancer properties

Three ternary copper(II) complexes, [Cu(phen)(L-phe)Cl]center dot 2H(2)O, [Cu(phen)(L-leu) Cl]center dot 41/2H(2)O, and [Cu(phen)(L-tyr)Cl]center dot 3H(2)O, and four binary copper(II) complexes, [Cu(phen)Cl-2], Cu(L-phe)(2)center dot 1/2H(2)O, Cu(L-leu)(2)center dot 1/2H(2)O, and Cu(L-tyr)(2)center dot H2O (where phen = 110-phenanthroline, L-phe = L-phenylalanine, L-tyr = L-tyrosine, L-leu = L-leucine and Cl- = chloride), were synthesized and characterized by elemental analysis, spectroscopic techniques (FTIR, UV-visible, fluorescence spectroscopy), magnetic susceptibility, molar conductivity, and lipophilicity measurement. X-ray diffraction determination of a single crystal of [Cu(phen)(L-tyr) Cl] showed two independent molecules in the asymmetric unit, each with the same distorted square pyramidal geometry about copper(II). p-Nitrosodimethylaniline assay revealed that the three ternary complexes were better inducers of reactive oxygen species over time than binary complexes, CuCl2, and free ligands. All the copper(II) complexes in this series inhibited the three proteolytic activities in the order Trypsin-like > Caspase-like > Chymotrypsin-like. In terms of anticancer properties, the copper(II)-phen complexes had GI50 values of less than 4 mu M against MCF-7, HepG2, CNE1 and A549 cancer cell lines, more potent than cisplatin.