Inhibition of human topoisomerase II by the antitumor metallocenes

The ability of antitumor active metallocenes Cp2MCl2, (M = Ti, V, Mo, Nb) and the biologically inactive derivative (MeCp)(2)TiCl2, to inhibit the relaxation of supercoiled plasmid DNA pBR322 by human topoisomerase II has been studied by gel electrophoresis. All metallocenes inhibit the enzyme with maximum inhibition observed at 2.0 mM (Cp2TiCl2), 3.0 mM (Cp2MoCl2), 0.2 mM (Cp2NbCl2), 0.25 mM (Cp2VCl2) and 2.0 mM (MeCpTiCl2). The implications for the mechanism of antitumor activity of the metallocene dihalides are discussed. (C) 2001 Elsevier Science B.V. All rights reserved.