Palladium(II) and platinum(II ) saccharinate complexes with bis(diphenylphosphino)methane/ ethane: synthesis, S-phase arrest and ROS- mediated apoptosis in human colon cancer cells
No Thumbnail Available
Date
2018-07-24
Journal Title
Journal ISSN
Volume Title
Publisher
Royal Society of Chemistry
Abstract
New neutral [M(sac)(2)(diphos)] and cationic [M(diphos)(2)](sac)(2) complexes, where M = Pd-II or Pt-II, sac = saccharinate, and diphos = 1,1-bis(diphenylphosphino)methane (dppm) or 1,2-bis(diphenylphosphino)ethane (dppe), were synthesized and structurally characterized. The anticancer activity of the complexes was investigated against MCF-7 (breast), A549 (lung), HCT116 (colon), DU145 (prostate) cancer and BEAS-2B (normal bronchial epithelial) cells. Neutral Pt-dppm (2) and Pd-dppe complexes (5) did not show any biological activity. The cationic Pd-dppe (7) complex displayed antiproliferative activity, while the rest of the complexes exhibited potent cytotoxicity compared with cisplatin. The active Pd(ii)/Pt(ii) complexes were then included in further studies including interaction with DNA/HSA, nuclease activity, cellular uptake and lipophilicity. The potent complexes induced the apoptotic cell death as probed through annexin V positivity and caspase activation. Mechanistic studies on HCT116 cells showed that the complexes cause cell cycle arrest at the DNA synthesis (S) phase and excessive generation of reactive oxygen species (ROS), damaging to both mitochondria and DNA.
Description
Keywords
Adsorptive stripping voltammetry, Thiosaccharinate tsac complexes, Ascites-carcinoma eac, DNA-binding agents, In-vitro, Crystal-structures, Antiproliferative activity, Molecular-mechanisms, Anticancer activity, Thermal-properties, Bioactivity, Cell death, Cytotoxicity, Diseases, DNA, Methane, Platinum compounds, Synthesis (chemical), Anti-proliferative activities, Anticancer activities, Apoptotic cell death, Caspase activation, Human colon cancer cells, Interaction with dnas, Mechanistic studies, Reactive oxygen species, Palladium compounds, Chemistry
Citation
İcsel, C. vd. (2018). ''Palladium(II) and platinum(II ) saccharinate complexes with bis(diphenylphosphino)methane/ ethane: synthesis, S-phase arrest and ROS- mediated apoptosis in human colon cancer cells''. Dalton Transactions, 47(33), 11397-11410.