De novo design and preparation of Copper(II)-based chemotherapeutic anticancer drug candidates with Boc-glycine and N,N -donor ligands: DNA binding, cleavage profile, and cytotoxic therapeutic response against MCF-7, PC-3, and HCT-116 cells

Two new copper(II) complexes [Cu(Boc-glycine)(2,2-bipyridyl) 2 ]NO 3 1 and [Cu(Boc-glycine) (1,10-phenanthroline) 2 ]NO 3 2 were prepared, and thoroughly characterized by multiple spectroscopic methods. The SC X-ray diffraction studies revealed that the complexes crystallized in triclinic (P 1) system with distorted square pyramidal and octahedral geometry in 1 and 2 , respectively. To predict the anticancer potential of the drug candidates 1 and 2 , binding studies with the ct-DNA were performed by using various complimentary biophysical methods. The drug candidates 1 and 2 interact strongly with DNA exhibiting 'hypochromic' effect in the absorbance bands at 300 nm implicating non-covalent intercalation binding mode that could be induced by the presence of strong recognition domain ligand (phen) which is known to 'wedge-in' in-between the bases of DNA helix. The intrinsic binding constant, K b values were quantified by employing Wolfe-Shimer equation, and were found to be 0.10(+/- 0.14) x 10 5 M -1 and 1.53 x 10 6 (+/- 0.1) M -1 , respectively, showing higher binding propensity of 2 as compared to 1 . pBR322 plasmid DNA cleavage studies of the complexes 1 and 2 showed that the complexes induced single-strand cleavage of DNA at a low concentration of 20 mu M and 15 mu M which mediated via an oxidative mechanism. The cytotoxicity activity of complexes was evaluated against MCF-7, PC-3, and HCT-116 cancer cells and the complexes displayed exceptionally good cytotoxicity against the tested cell lines ( 1 , HCT-116:IC 50 = 0.6 +/- 0.02 mu M and 2 , MCF-7:IC 50 = 1.91 +/- 0.1 mu M).