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 p repared, where L are the diamine ligands N-[2-[(aminoethyl)amino]ethyl]-phe nazine-1-carboxamide, N-[3-[(2-aminoethyl)amino]propyl]-phenazine-1-carboxa mide, N-[4-[(2-aminoethyl)amino]butyl]-phenazine- 1-carboxamide and N-[5-[( aminoethyl)amino]pentyl]-phenazine-1-carboxamide. Measurements of the timec ourse of unwinding of supercoiled pUC19 plasmid DNA by the phenazine comple xes PtLCl2 reveal that the presence of the intercalator leads to enhanced r ates of DNA platination when compared with the complex Pt(en)Cl-2. The plat inum(II) complexes where the polymethylene linker chain contains three, fou r or five carbon atoms are considerably more cytotoxic against murine P388/ W than either cisplatin, Pt(en)Cl-2, or the metal-free ligands themselves. (C) 2000 Elsevier Science S.A. All rights reserved.