DNA targeted platinum complexes: Synthesis, cytotoxicity and DNA interactions of cis-dichloroplatinum(II) complexes tethered to phenazine-1- carboxamides

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. (C) 2000 Elsevier Science S.A.