title: Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence.
abstract: A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the N^C^N-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the C^N^N-coordinated platinum complex based on 6-phenyl-2,2'-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by N^C^N- and C^N^N-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the N^C^N-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed that the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis were studied by western blot analysis and the activation of PARP via caspase 7 was observed.
authors: Department of Chemistry, East Carolina University, Greenville, NC 27858, United States.
authors: Dileep A K
authors: DA
authors: Vezzu
authors: Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States.
authors: Qun
authors: Q
authors: Lu
authors: Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, United States. Electronic address: cheny@ecu.edu.
authors: Yan-Hua
authors: YH
authors: Chen
authors: Department of Chemistry, East Carolina University, Greenville, NC 27858, United States. Electronic address: huos@ecu.edu.
authors: Shouquan
authors: S
authors: Huo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D010984:Platinum / Q000737:chemistry*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D011725:Pyridines; D010984:Platinum; D011065:Poly(ADP-ribose) Polymerases; D053179:Caspase 7
keywords: Anticancer; Cyclometalated complex; Cytotoxicity; DNA binding; Platinum