Novel functionalized thiosemicarbazone ligands and their Pd(II) complexes: synthesis, characterization, antibacterial and cytotoxic activities

Palladium (II) complexes of coumarinyl thiosemicarbazone derivatives as 1-(1-(2-oxo-2H-chromen-3-yl) ethylidene) thiosemicarbazone (OCETh), 1-(1-(6-bromo-2-oxo-2H-chromen-3-yl) ethylidene) thiosemicarbazone (BOCETh) and 1-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene) thiosemicarbazone (NOCETh) were prepared. The complexes have the formula [Pd (L) Cl]. DMF, where DMF=dimethylformamide and L=OCETh, BOCETh or NOCETh. The studied ligands act as a tridentate ligand by using azomethine nitrogen, carbonyl oxygen and thiol sulfur as a monoanion center of donation. The characterization part was carried out using different physicochemical tools such as elemental analysis, IR, UV-visible, mass, magnetic measurement and molar conductance techniques. The theoretical conformational structure analyses were performed using density functional theory for ligands and complexes at B3LYP functional with 6-31++G(d,p) basis set for ligands and LANL2DZ basis set for complexes. The charge distribution within the ligands and its pd(II) complexes was calculated using Mulliken population analysis of (MPA) and natural population analysis (NPA). The prepared pd(II) complexes showed a satisfactory cytotoxic effect results against the human colon cancer cell line (HCT-116). Additionally, docking study was performed on colon cancer target cyclin-dependent kinase-2 to understand the cytotoxic modes of actions by the active compounds. The antibacterial activity was tested against some types of Gram-positive and negative bacteria. Molecular docking investigation proved that all synthesized compounds had interesting interactions with the active site amino acids of glucosamine-6-phosphate synthase. Density functional theory was used to theoretically analyze the conformational structure of the ligands and Pd (II) complexes.