RESUMO
The first examples of platinum(II)-amine complexes containing a dicarba-closo-dodecaborane(12) (carborane) moiety are described; preliminary in vitro DNA-binding experiments indicate that the complexes are capable of targetting plasmid DNA.
Assuntos
Antineoplásicos/química , Antineoplásicos/metabolismo , Compostos de Boro/química , Compostos de Boro/metabolismo , DNA/metabolismo , Desenho de Fármacos , Compostos Organoplatínicos/química , Compostos Organoplatínicos/metabolismo , Terapia por Captura de Nêutron de Boro , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/metabolismo , Espectroscopia de Ressonância Magnética , PlasmídeosRESUMO
Some DNA-binding experiments employing a selected number of novel dinuclear platinum complexes with the 4,4'-dipyrazolylmethane (dpzm) ligand are reported. A DNA-cleavage assay using Eco RI and Bam HI restriction endonucleases to probe the binding of the complexes at or near their unique restriction sequences of pUC9 DNA has been examined. The complex beta-[Cl2Pt(dpzm)2PtCl2] has a greater affinity for DNA at the Eco RI restriction sequence over the Bam HI site. To our knowledge, the preferential inhibition of Eco RI activity is unprecedented for any platinum species reported to date. Further, the dinuclear complexes beta-[Cl2Pt(dpzm)2PtCl2], beta-[Cl4Pt(dpzm)2PtCl4] x 0.5dmf x 0.5H2O and [Cl4Pt(dpzm)2PtCl2] are capable of inhibiting Eco RI activity to a far greater extent than the platinum anticancer drug cis-[PtCl2(NH3)2] (cisplatin). The in vivo and in vitro anticancer properties of some of the platinum complexes are also described. The complexes alpha-[Cl2Pt(dpzm)2PtCl2] x 0.5dmf and beta-[Cl2Pt(dpzm)2PtCl2] display significant activity against P388 lymphocytic leukemia in mice.
