Novel Palladium(II) β-Diketonate Complexes: Synthesis, Dual Antimicrobial/Anticancer Activity, and Molecular Insights into DNA/Protein Interactions

This study reports the synthesis and biological evaluation of four novel palladium(II) complexes (B1–B4) with O,O-bidentate β-diketo ester ligands. Spectroscopic characterization confirmed their structures, while biological assays revealed substituent-dependent activity. Complexes B3 and B4 showed the most consistent antimicrobial activity, with minimum inhibitory concentrations (MICs) of 312–1200 μM across the tested microorganisms. B3 exhibited the highest antiproliferative potency, with IC50 values of 2.3, 5.2, and 5.4 μM against K-562, HeLa, and HaCaT cells, respectively. However, its selectivity varied with the cell model, reaching a selectivity index (SI) of 5.17 against K-562 cells relative to MRC-5 fibroblasts and 2.35 relative to HaCaT cells. B2 showed a more moderate activity profile, with some selectivity towards K-562 cells. Flow-cytometric analysis revealed increased sub-G0/G1 populations following treatment, consistent with the induction of apoptosis. Biophysical assays and molecular docking indicated structure-dependent interactions with DNA, while fluorescence studies revealed differences in the apparent binding affinities of the complexes toward human serum albumin (HSA). These findings highlight the influence of ligand structure on the biological activity and biomolecular interactions of palladium(II) complexes, identifying B3 as the most promising candidate for further investigation based on its antiproliferative potency and selectivity.