title: DNA targeted platinum complexes: synthesis, cytotoxicity and DNA interactions of cis-dichloroplatinum(II) complexes tethered to phenazine-1-carboxamides.
abstract: A series of intercalator-tethered platinum(II) complexes PtLCl2 have been prepared, where L are the diamine ligands N-[2-[(aminoethyl)amino]ethyl]-phenazine-1-carboxamide, N-[3-[(2-aminoethyl)amino]propyl]-phenazine-1-carboxamide, N-[4-[(2-aminoethyl)amino]butyl]-phenazine-1-carboxamide and N-[5-[(aminoethyl)amino]pentyl]-phenazine-1-carboxamide. Measurements of the time-course of unwinding of supercoiled pUC19 plasmid DNA by the phenazine complexes PtLCl2 reveal that the presence of the intercalator leads to enhanced rates of DNA platination when compared with the complex Pt(en)Cl2. The platinum(II) complexes where the polymethylene linker chain contains three, four or five carbon atoms are considerably more cytotoxic against murine P388/W than either cisplatin, Pt(en)Cl2, or the metal-free ligands themselves.
authors.affiliation: School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: L C
authors.initials: LC
authors.lastname: Perrin
authors.forename: P D
authors.initials: PD
authors.lastname: Prenzler
authors.forename: C
authors.initials: C
authors.lastname: Cullinane
authors.forename: D R
authors.initials: DR
authors.lastname: Phillips
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
authors.forename: W D
authors.initials: WD
authors.lastname: McFadyen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives*; D004926:Escherichia coli / Q000235:genetics; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D010957:Plasmids / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007364:Intercalating Agents; D009944:Organoplatinum Compounds; D010619:Phenazines; D002945:Cisplatin