Design, synthesis and characterization of novel chromone based-copper(II) antitumor agents with N,N-donor ligands comparative DNA/RNA binding profile and cytotoxicity
Résumé
A series of new chromone based-Cu(ii) complexes 1-3 derived from bioactive pharmacophore, 3-formylchromone and ,-donor ligands , 1,10-phenanthroline, 2,2'-bipyridine and 1,2-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 1̄ space group with square pyramidal geometry around the Cu(ii) center. Comparative 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 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 ) 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, 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 GI value < 10 μg mL (<20 μM).
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