Design, synthesis and characterization of novel chromone based-copper(ii) antitumor agents with N,N-donor ligands: comparative DNA/RNA binding profile and cytotoxicity

Abstract

A series of new chromone based-Cu(II) complexes 1–3 derived from bioactive pharmacophore, 3-formylchromone and N,N-donor ligands viz., 1,10-phenanthroline, 2,2′-bipyridine and 1R,2R-DACH were synthesized as potential antitumor agents and thoroughly characterized by UV-vis, FT-IR, EPR, ESI-MS and elemental analysis. Single X-crystal diffraction studies of complex 2 revealed triclinic P space group with square pyramidal geometry around the Cu(II) center. Comparative in vitro binding studies with ct-DNA and tRNA were carried out using absorption and emission titration experiments which revealed intercalative mode of binding with higher binding propensity of complexes 1–3 towards tRNA as compared to ct-DNA. Additionally, complex 1 exhibited high binding affinity among all the three complexes due to the involvement of phen co-ligands via π-stacking interactions in between nucleic acid base pairs. Furthermore, Hirshfeld surface analysis was carried out for complex 2 to investigate various intra and intermolecular non-covalent interactions (H-bonding, C–H⋯π etc.) accountable for stabilization of crystal lattice. The cleavage activity of complex 1 was performed by gel electrophoretic assay with pBR322 DNA and tRNA which revealed efficient DNA/tRNA cleaving ability of complex, suggesting tRNA cleavage both concentration and time dependent. Furthermore, in vitro cytotoxic activity of complexes 1–3 on a selected panel of human cancer cell lines was performed which revealed that all three complexes exhibited remarkably good cytotoxic activity with GI₅₀ value < 10 μg mL⁻¹ (<20 μM).