Differential Cytotoxic Activity of a New Cationic Pd(II) Coordination Compound with N4-Tetradentate Hybrid Ligand in Cancer Cell Lines

Authors : Merve ERKISA GENEL, Selin SELVİ, Ismail YILMAZ, Remzi Okan AKAR, İlhan YAYLIM, Abdurrahman ŞENGÜL, Engin ULUKAYA

Pages : 188-201

Doi:10.26650/experimed.1188586

View : 36 | Download : 9

Publication Date : 2022-12-31

Article Type : Research Paper

Abstract :Objective: Successful cancer treatment still requires the discovery of novel compounds that hold promise for chemotherapeutics. The objective of this study was to examine the effectiveness of a newly synthesized cationic palladiuminsert ignore into journalissuearticles values(II); coordination compound that functions via several pathways to provide an efficient therapeutic option for various cancer cells. Materials and Methods: A new cationic palladiuminsert ignore into journalissuearticles values(II); coordination compound, [Pdinsert ignore into journalissuearticles values(L);]Cl2·H2O, denoted as Complex 1, where the ligand L is the compound 6,6\`-bisinsert ignore into journalissuearticles values(NH-benzimidazol-2-yl);-2,2\`-bipyridine);, was synthesized and characterized by the attenuated total reflectance insert ignore into journalissuearticles values(ATR); - fourier-transform infrared spectroscopy insert ignore into journalissuearticles values(FT-IR);, proton nuclear magnetic resonance insert ignore into journalissuearticles values(1H NMR);, electrospray ionization mass spectrometry insert ignore into journalissuearticles values(ESI-MS);, and carbon-hydrogen-nitrogen insert ignore into journalissuearticles values(CHN); analyses. The density functional theory insert ignore into journalissuearticles values(DFT); calculations show the coordination sphere around the metal center in Complex 1 to be made up of tertiary N atoms of the pyridine insert ignore into journalissuearticles values(py); and benzimidazole insert ignore into journalissuearticles values(bim); rings completing the square-planar geometry with significant distortion. The anti-growth/cytotoxic activity of the complex was determined using the sulforhodamine B insert ignore into journalissuearticles values(SRB); and adenosine triphosphate insert ignore into journalissuearticles values(ATP); viability assays for 24 and 48 h in vitro. The study evaluates the determinations for annexin V-propidium iodide insert ignore into journalissuearticles values(PI); positivity, mitochondrial membrane potential loss, Bcl-2 protein inactivation, and deoxyribonucleic acid insert ignore into journalissuearticles values(DNA); damage to investigate the cell death mode and its partial mechanism. Results: Complex 1 caused cytotoxicity in a dose-dependent manner in all the cell lines used, with IC50 values ranging from 2.6-8.8 μM for 48 h. Among the cancer models, colon and breast cancer cell lines underwent cell death by well-described apoptosis through the intrinsic pathway involving the mitochondria. However, the other cell lines did not show such a cell death modality. This implies that differential cell death modes operate based on the cancer type. Conclusion: For the treatment of breast and colon cancers, the complex 1 appears to be a unique, promising complex. Therefore, complex 1 deserves further attention for proof of concept in animal models.
Keywords : Palladium complexes, N4 donor ligand, benzimidazole, bipyridine, apoptosis, anticancer effect

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