Chromone-Appended Zn(II) tRNA-Targeted Potential Anticancer Chemotherapeutic Agent: Structural Details, in vitro ct-DNA/tRNA Binding, Cytotoxicity Studies And Antioxidant Activity
Résumé
A 3-formyl-chromone-appended zinc(II) intercalator drug candidate of the formulation [bis(chromone)(H (2) O)(2) Zn(II)] was prepared as a potent anticancer agent and thoroughly characterized by multi-spectroscopic and single X-ray crystallographic studies. Preliminary binding studies of complex 1 with ct-DNA/tRNA were carried out employing various complementary biophysical techniques and the corroborative results of these experiments suggested strong binding propensity via intercalation binding mode towards ct-DNA/tRNA therapeutic targets, with higher preference for tRNA as quantified by binding constant {K-b , K and K-sv } parameters. The cleavage studies with pBR322 DNA were performed which implied that 1 cleaved the DNA by hydrolytic cleavage pathway which was further validated by T4 religation assay. Moreover, 1 was found to exhibit the tRNA cleavage behavior in a concentration and time-dependent manner. The cytotoxicity of complex 1 was evaluated against Huh-7, DU-145 and the PNT2 cell lines by MTT assay. A dose-dependent growth inhibition of the Huh-7 and DU-145 cells at low micromolar concentrations was observed and in another set of experiments, lipid peroxidation and glutathione (GSH) depletion were induced in the presence of the tested drug candidate. Interestingly, drug candidate 1 demonstrated selective cytotoxic activity for the DU-145 cancer cell line with LC50 value of 3.2 mu M which was further visualized by confocal microscopy.