Dalton transactions (Cambridge, England : 2003)

Mechanistic insights into a novel chromone-appended Cu(II) anticancer drug entity: in vitro binding profile with DNA/RNA substrates and cytotoxic activity against MCF-7 and HepG2 cancer cells.

PMID 25970097


A new chromone-appended Cu(ii) drug entity () was designed and synthesized as a potential anticancer chemotherapeutic agent. The structural elucidation was carried out thoroughly by elemental analysis, FT-IR, EPR, ESI-MS and single crystal X-ray crystallography. Complex resulted from the in situ methoxylation reaction of the 3-formylchromone ligand and its subsequent complexation with the copper nitrate salt in a 2 : 1 ratio, respectively. crystallized in the monoclinic P21/c space group possessing the lattice parameters, a = 8.75 Å, b = 5.07 Å, c = 26.22 Å, α = γ = 90°, β = 96.3° per unit cell. Furthermore, in vitro interaction studies of with ct-DNA and tRNA were carried out which suggested more avid binding propensity towards the RNA target via intercalative mode, which was reflected from its Kb, K and Ksv values. The gel electrophoretic mobility assay was carried out on the pBR322 plasmid DNA substrate, to ascertain the cleaving ability and the mechanistic pathway in the presence of additives, and the results revealed the efficient cleaving ability of via the oxidative pathway. In vitro cell growth inhibition via the MTT assay was carried out to evaluate the cytotoxicity of complex and IC50 values were found to be in the range of 5-10 μg mL(-1) in HepG2 and MCF-7 cancer cell lines, which were found to be much lower than the IC50 values of previously reported similar Cu(ii) complexes. Additionally, in the presence of , reactive oxygen species (ROS) and thiobarbituric acid reactive substance (TBARS) levels in the tested cancer cell lines increased significantly, coupled with reduced glutathione (GSH) levels. Thus, our results suggested that ROS plays an important role in cell apoptosis induced by the Cu(ii) complex and validates its potential to act as a robust anticancer drug entity.