Synthesis, Physicochemical Characterization, Biological Evaluation, In Silico and Molecular Docking Studies of Pd(II) Complexes with P, S-Donor Ligands

One homoleptic (1) and three heteroleptic (2-4) palladium(II) complexes were synthesized and characterized by various physicochemical techniques, i.e., elemental analysis, FTIR, Raman spectroscopy, H-1, C-13, and P-31 NMR. Compound 1 was also confirmed by single crystal XRD, showing a slightly distorted square planar geometry. The antibacterial results obtained via the agar-well diffusion method for compound 1 were maximum among the screen compounds. All the compounds have shown good to significant antibacterial results against the tested bacterial strains, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, except 2 against Klebsiella pneumonia. Similarly, the molecular docking study of compound 3 has shown the best affinity with binding energy scores of -8.6569, -6.5716, and -7.6966 kcal/mol against Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, respectively. Compound 2 has exhibited the highest activity (3.67 & mu;M), followed by compound 3 (4.57 & mu;M), 1 (6.94 & mu;M), and 4 (21.7 & mu;M) against the DU145 human prostate cancer cell line using the sulforhodamine B (SRB) method as compared to cisplatin (>200 & mu;M). The highest docking score was obtained for compounds 2 (-7.5148 kcal/mol) and 3 (-7.0343 kcal/mol). Compound 2 shows that the Cl atom of the compound acts as a chain side acceptor for the DR5 receptor residue Asp B218 and the pyridine ring is involved in interaction with the Tyr A50 residue via arene-H, while Compound 3 interacts with the Asp B218 residue via the Cl atom. The physicochemical parameters determined by the SwissADME webserver revealed that no blood-brain barrier (BBB) permeation is predicted for all four compounds, while gastrointestinal absorption is low for compound 1 and high for the rest of the compounds (2-4). As concluding remarks based on the obtained in vitro biological results, the evaluated compounds after in vivo studies might be a good choice for future antibiotics and anticancer agents.

Automated summary

One homoleptic and three heteroleptic palladium(II) complexes were synthesized and characterized. The antibacterial results showed that compound 1 had the highest activity among the screened compounds. Compound 3 exhibited the best affinity in the molecular docking study. In the anticancer evaluation, compound 2 showed the highest activity against the DU145 human prostate cancer cell line. The physicochemical parameters suggested that the evaluated compounds may be potential candidates for future antibiotics and anticancer agents.