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

Hizbullah Khan; Muhammad Sirajuddin; Amin Badshah; Sajjad Ahmad; Muhammad Bilal; Syed Muhammad Salman; Ian S Butler; Tanveer A Wani; Seema Zargar

doi:10.3390/ph16060806

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

Pharmaceuticals (Basel). 2023 May 29;16(6):806. doi: 10.3390/ph16060806.

Authors

Hizbullah Khan¹, Muhammad Sirajuddin¹, Amin Badshah², Sajjad Ahmad³, Muhammad Bilal⁴, Syed Muhammad Salman⁵, Ian S Butler⁶, Tanveer A Wani⁷, Seema Zargar⁸

Affiliations

¹ Department of Chemistry, University of Science and Technology, Bannu 28100, Pakistan.
² Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
³ Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan.
⁴ Department of Chemistry, Kohat University of Science and Technology, Kohat 26000, Pakistan.
⁵ Department of Chemistry, Islamia College University, Peshawar 25120, Pakistan.
⁶ Department of Chemistry, University of McGill, Montreal, QC H3A 0B8, Canada.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
⁸ Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11451, Saudi Arabia.

Abstract

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, ¹H, ¹³C, and ³¹P 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 µM), followed by compound 3 (4.57 µM), 1 (6.94 µM), and 4 (21.7 µM) against the DU145 human prostate cancer cell line using the sulforhodamine B (SRB) method as compared to cisplatin (>200 µM). 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.

Keywords: Pd(II) complexes; X-ray structure; antibacterial activity; antitumor activity; in silico study; molecular docking.

Abstract

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