Journal
CANADIAN JOURNAL OF CHEMISTRY
Volume 83, Issue 6-7, Pages 969-979Publisher
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/V05-110
Keywords
anticancer; metallointercalator; cyclometallation; palladium; platinum; cytotoxicity
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Reaction of a series of nitrogen donor ligands (1-phenylpyrazoles, 2-phenylpyridine, benzo[h] quinoline, 1(2'-pyridyl) indole, 1-phenylindazole, and 2-phenylindazole) with palladium(II) and platinum( II) salts gave complexes where ortho-metallation had occurred resulting in bidentate binding to the metal centres through N and C atoms. These cyclometallated products were isolated as mu-chloro dimers. Subsequent treatment of these mu-chloro dimers with chelating diamines such as 1,2-ethanediamine converted them into 14 cationic (1+) complexes. Analogous coordination mixed ligand complexes ( charge 2+) were prepared by reaction of dichloro(1,2-ethanediamine-N,N') palladium(II) with aromatic diamines such as 2-(1'-pyrazolyl) pyridine, 2,2'-bipyridine, and 1,10-phenanthroline. The complexes exhibited growth inhibitory activity against L1210 mouse leukaemia cells in vitro over a wide concentration range; in general, the cyclometallated complexes were more active than the mixed ligand complexes, although one cyclometallated organoplatinum complex was less active than the mixed ligand analogue. Substitution around the periphery of the aromatic ligands also resulted in increased activity. One complex, derived from 1-(2'-pyridyl)indole, was tested in vivo and showed no significant antitumour inhibition against P388 leukaemia at doses below toxic levels.
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