A1 Journal article (refereed)
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 (2024)

Ragheb, M. A., Soliman, M. H., Abdelhamid, I. A., Shoukry, M. M., Haukka, M., & Ragab, M. S. (2024). 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. Journal of Inorganic Biochemistry, 253, Article 112488. https://doi.org/10.1016/j.jinorgbio.2024.112488

JYU authors or editors

Publication details

All authors or editors: Ragheb, Mohamed A.; Soliman, Marwa H.; Abdelhamid, Ismail A.; Shoukry, Mohamed M.; Haukka, Matti; Ragab, Mona S.

Journal or series: Journal of Inorganic Biochemistry

ISSN: 0162-0134

eISSN: 1873-3344

Publication year: 2024

Volume: 253

Article number: 112488

Publisher: Elsevier

Publication country: United States

Publication language: English

DOI: https://doi.org/10.1016/j.jinorgbio.2024.112488

Publication open access: Not open

Publication channel open access: 

Abstract

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH2)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)(OH2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH2)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)(OH2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC50 = 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)(OH2)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)(OH2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer.

Keywords: antimicrobial compounds

Contributing organizations

Ministry reporting: Yes

VIRTA submission year: 2024

Preliminary JUFO rating: 1