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)2TiCl2, 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.
School of Chemistry, University of Sydney, NSW, Australia.
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000494:pharmacology*; D010957:Plasmids; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D059005:Topoisomerase II Inhibitors; D004247:DNA; D004250:DNA Topoisomerases, Type II