Anticancer behaviour of 2,2′-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione)-based palladium(II) complex and its DNA, BSA binding propensity and DFT study.

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH 2)Cl] complex (where L = 2,2′-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione) as a novel promising anticancer candidate. The complex was characterized by single-crystal X-ray diffraction and other various spectroscopic techniques. Besides, the optimized structure was determined through DFT calculations revealing that the coordination geometry of [Pd(L)(OH 2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH 2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH 2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH 2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH 2)Cl] complex exhibited a potent antiproliferative potential compared to its ligand against different human cancer cells (A549, HCT116, MDA-MB-231, and HepG2) with less toxic effect against normal cells (WI-38). Additionally, [ Pd(L)(OH 2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC 50 = 11 ± 1 μM) through suppressing their colony-forming capabilities and triggering apoptosis and cell cycle arrest at S phase. Quantitative PCR analysis revealed a remarkable upregulation of the mRNA expression level of p53 and caspase-3 by 4.8- and 5.9-fold, respectively, relative to control. Remarkable binding properties and non-covalent interactions between L and its [Pd(L)(OH 2)Cl] complex with the binding sites of different receptors including CDK2, MurE ligase, DNA, and BSA were established using molecular docking. Based on our results, [Pd(L)(OH 2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer. [Pd(L)(OH 2)Cl] complex was synthesized and characterized by X-ray crystallography. [Pd(L)(OH 2)Cl] complex binding potentials towards different receptors were evaluated using docking. Anticancer activity was evaluated using MTT, apoptotic, and cell cycle assays. Caspase-3 and p53 expression levels were upregulated by 4.8- and 5.9-fold compared to control cells using qRT-PCR analysis. [Display omitted] • A new palladium complex was synthesized and confirmed through X-ray investigation. • [Pd(L)(OH 2)Cl] complex showed good antibacterial effects and DNA/BSA-binding potentials. • The complex revealed a potent cytotoxicity against different human cancer cells. • Caspase-3 and p53 expression levels were significantly upregulated using qPCR analysis. • Docking showed binding properties of [Pd(L)(OH 2)Cl] complex towards different receptors. [ABSTRACT FROM AUTHOR]