Promising in vitro and in silico biological activity of tetradentate Schiff base copper(ii) complexes with a propylenediamine bridge

Abstract

The molecular structures of six neutral copper(II) complexes with propylenediamine bridges and different terminal groups have been reported and evaluated. Different antioxidant tests were performed on these complexes. Additionally, the antibacterial and antifungal activities of the investigated compounds were assessed. The study was complemented with data on their interaction with human serum albumin (HSA) and evaluated using spectroscopic fluorescence techniques. The copper(II) complexes were found to bind to HSA at multiple sites (n = 0.82–1.72), displaying relatively high binding constants on the order of K_a = (4.8–8.8) × 10⁴ M⁻¹. Furthermore, binding constants calculated from microscale thermophoresis (MST) data were within the range of 1.27 × 10⁴–1.13 × 10⁵ M⁻¹; these results correlated well with the above K_a values obtained by fluorimetry. Molecular docking simulations were employed to study the ability of the complexes to bind to target macromolecules, such as HSA and DNA. As a significant addition to understanding their biological behavior, an MTT assay was performed to investigate the cytotoxicity of the complexes. The antiproliferative activity of the investigated copper(II) complexes with propylenediamine ligands, along with cisplatin as a reference compound, was evaluated in two human cancer cell lines (LS-174 and MCF-7) and one normal cell line (MRC-5). The obtained results are discussed, providing the structure–activity relationship of the copper(II) complexes with Schiff base tetradentate ligands.