Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 81, Issue 1-2, Pages 111-117Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0162-0134(00)00092-1
Keywords
phenazine-1-carboxamides; cis-dichloroplatinum (II); unwinding; DNA; cytotoxicity
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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 timecourse 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)Cl-2. 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)Cl-2, or the metal-free ligands themselves. (C) 2000 Elsevier Science S.A. All rights reserved.
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