text: The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo- and imino-pyridine anticancer complexes: control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway.
  Organometallic half-sandwich complexes [M(p-cymene)(azo/imino-pyridine)X](+) where M = Ru(II) or Os(II) and X ═ Cl or I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido complexes more potent than the chlorido analogues, but they are not cross-resistant with the clinical platinum drugs cisplatin and oxaliplatin. They are also more selective for cancer cells versus normal cells (fibroblasts) and show high accumulation in cell membranes. They arrest cell growth in G1 phase in contrast to cisplatin (S phase) with a high incidence of late-stage apoptosis. The iodido complexes retain potency in p53 mutant colon cells. All complexes activate caspase 3. In general, antiproliferative activity is greatly enhanced by low levels of the glutathione synthase inhibitor l-buthionine sulfoxime. The work illustrates how subtle changes to the design of low-spin d(6) metal complexes can lead to major changes in cellular metabolism and to potent complexes with novel mechanisms of anticancer activity.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: cisplatin iodido glutathione l-buthionine sulfoxime M = Ru(II) or Os(II) iodido chlorido ruthenium osmium arene azo- and imino-pyridine p53 caspase 3 X ═ Cl or I glutathione synthase p53 Cl I iodido chlorido platinum cisplatin oxaliplatin [M(p-cymene)(azo/imino-pyridine)X](+)