Design, synthesis, ligand’s scaffold variation and structure elucidation of Cu(II) complexes; In vitro DNA binding, morphological studies and their anticancer activity

Abstract

Two new copper(II) complexes, Cu[(L)2(X)] (1) and Cu[(L)(X)2] (2) where L = 1,10-phenanthroline and X = (2-pyrimidylthio)-acetic acid (PTAA), have been synthesized and characterized utilizing physico-chemical techniques and single X-ray crystallography. Various techniques, like absorption, emission and CD spectroscopy, CV and SEM, were applied to explore drug-DNA interactions and their collaborative results revealed an electrostatic or groove binding mode of interaction of both drug candidates with ct-DNA. In addition, pBR322 cleavage activities were carried out which suggested significant oxidative cleavage with complex 1 compared to complex 2. Moreover, in vitro cytotoxic studies of complexes 1 and 2 were performed by an SRB assay against MCF-7, MDA-MB-231 and Hop-62 cancer cell lines. Both complexes showed good cytotoxic activity against all the cancer cell lines, with GI50 values < 10 μM. Interestingly, complex 1 exhibited a more efficient cytotoxic activity against MDA-MB-231 and HOP-62, even greater than that of the standard drug Adriamycin. Additionally, molecular docking studies were carried out which gave results that are in good agreement with the spectroscopic results. Furthermore, DFT calculations were performed and electrostatic maps were generated to shed light on the stability, charge density and reactivity of these complexes.