Functional copper complexes with benzofurans tridentate ligand: Synthesis, crystal structure, DNA binding and anticancer studies

Abstract

Metal complexes, particularly copper(II) complexes, are often used as anticancer drugs due to their ability to generate reactive oxygen species (ROS) in cells. Four copper(II) complexes have been designed based on ligands for triplet pyridine derivatives (complexes 1-4), and their structures have been determined using X-ray single crystal analysis. The interactions of these complexes with calf thymus DNA (CT-DNA) have been investigated using various techniques, including UV-vis absorption, viscosity measurements, and circular dichroism spectroscopy. The results indicate that complexes 1-4 strongly interact with DNA through partial intercalations. Further investigation using agarose gel electrophoresis shows that all four complexes can cleave pBR322 DNA in the presence of ascorbic acid as a reducing agent, and the DNA cleavage mechanism is through the generation of singlet oxygen (¹O₂). In vitro anticancer activities of these complexes have been evaluated using A549, MDA-MB-231, HeLa, and HepG2 cells. The calculated IC₅₀ values indicate significant efficacy against cancer cells. Additionally, AO/EB staining assays reveal that these complexes induce cell apoptosis in HeLa cell line.

Keywords: Apoptosis; Chemical nuclease; Copper complex; Cytotoxicity; DNA binding; DNA cleavage.