title: Tumor cytotoxicity of 5,6-dimethyl-1,10-phenanthroline and its corresponding gold(III) complex.
abstract: A gold(III) complex possessing 5,6-dimethyl-1,10-phenanthroline (5,6DMP) was synthesized and fully characterized using standard spectroscopic techniques, as well as X-ray crystallography and elemental analysis. The complex [(5,6DMP)AuCl(2)][BF(4)] (2) was found to possess a distorted square planar geometry about the gold(III) center, commonplace for d(8) Au(III) cations possessing sterically un-hindered polypyridyl ligands. Compound 2 was evaluated for its potential use as an anticancer therapeutic. It was determined that the complex is stable in phosphate buffer over a 24-hour period, thought it does undergo rapid reduction in the presence of equimolar amounts of reduced glutathione (GSH) and ascorbic acid. The DNA binding and in vitro tumor cytotoxicity of the title compound 2 were also determined. It was found to undergo weak and reversible binding to calf thymus DNA, and was more cytotoxic towards a panel of human cancer cell lines than the commonly used chemotherapy agent cisplatin. Cytotoxicity experiments with the free 5,6DMP ligand indicate that the ligand has IC(50) values that are slightly lower than those observed for the gold complex (2), and coupled with the fact that the ligand appears to be released from the gold(III) metal center in reducing environments, this suggests the ligand itself may play an important role in the antitumor activity of the parent gold complex.
authors: Emory University, Department of Chemistry, Atlanta, GA, United States.
authors: Alexander N
authors: AN
authors: Wein
authors: Adam T
authors: AT
authors: Stockhausen
authors: Kenneth I
authors: KI
authors: Hardcastle
authors: M Reza
authors: MR
authors: Saadein
authors: Shifang Bruce
authors: SB
authors: Peng
authors: Dongsheng
authors: D
authors: Wang
authors: Dong M
authors: DM
authors: Shin
authors: Zhuo Georgia
authors: ZG
authors: Chen
authors: Jack F
authors: JF
authors: Eichler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry* / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D050607:Organogold Compounds / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D008024:Ligands; D050607:Organogold Compounds; D006046:Gold; D004247:DNA; C427203:calf thymus DNA; D005978:Glutathione