RESUMO
This paper studies the anticancer potency of dendritic poly(aryl ether)-substituted polypyridyl ligand-based ruthenium(II) coordination entities. The dendritic coordination entities were successfully designed, synthesized, and characterized by different spectral methods such as Fourier transform infrared (FTIR), 1H and 13C- NMR, and mass spectrometry. Further, to understand the structure and solvation behavior of the coordination entities, we performed all-atom molecular dynamics (MD) simulations. The behavior, configuration, and size of the coordination entities in DMSO and water were studied by calculating the radius of gyration (Rg) and solvent-accessible surface area (SASA). The MTT assay was used to assess the in vitro cytotoxicity of all of the coordination entities against cancerous A549 (lung cancer cells), MDA MB 231 (breast cancer cells), and HepG2 (liver cancer cells) and was found to be good with comparable IC50 values with respect to the standard drug cisplatin. The coordination entities exhibited dose dependence, and the highest activity was shown against HepG2 cell lines in comparison to the other cancer cell lines. In addition, fluorescence staining studies, such as AO/EB, DAPI, and cell death analysis by PI staining, were performed on the coordination entities to understand the apoptosis mechanism. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays confirmed apoptosis in cancer cells via the mitochondrial pathway. The DNA fragmentation assay was done followed by molecular docking analysis with DNA executed to strengthen and support the experimental observations.
