Synthesis, spectroscopic characterization, biological activity, DFT and molecular docking study of novel 4-hydroxycoumarine derivatives and corresponding palladium(II) complexes

In the present manuscript, palladium(II) complexes (C1, C2) with newly synthesized coumarine ligands 3-(1-((3-chlorophenyl)amino)ethylidene)-chroman-2,4-dione (L1) and 3-(1-((4-chlorophenyl)amino)ethylidene)chroman-2,4-dione (L2) were prepared and structurally characterized by spectroscopic techniques (FT-IR, H-1 NMR, C-13 NMR) in combination with elemental analysis and theoretical methods (DFT). The structures of all compounds were fully optimized using the B3LYP-D3BJ theoretical method. Cytotoxic activity of investigated compounds was tested against two cells lines (human colorectal carcinoma, HCT-116, and human fibroblast lung MRC-5), while their antimicrobial activity was screened against nine strains of pathogenic bacteria, five mould species and two yeast species. Unfortunately, their cytotoxic and antibacterial activities were weak. Docking studies for all compounds with epidermal growth factor receptor (EGFR) were performed. It was found that hydrophobic interactions that include chlorine atom have somewhat lower values of the pairwise interaction energies compared to the purely hydrophobic interactions. In addition, it was found the chlorine atom in the para position contributes to the slightly higher binding free energy and lower values of constant of inhibition.