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.

作者: Isolda Romero-Canelón , Luca Salassa , Peter J. Sadler

DOI: 10.1021/JM3017442

关键词:

摘要: Organometallic half-sandwich complexes [M(p-cymene)(azo/imino-pyridine)X]+ where M = RuII or OsII and X ═ Cl I, exhibit potent antiproliferative activity toward a range of cancer cells. Not only are the iodido more than chlorido analogues, but they not cross-resistant with clinical platinum drugs cisplatin oxaliplatin. They also selective for cells versus normal (fibroblasts) show high accumulation in cell membranes. arrest growth G1 phase contrast to (S phase) incidence late-stage apoptosis. The retain potency p53 mutant colon All activate caspase 3. In general, is greatly enhanced by low levels glutathione synthase inhibitor l-buthionine sulfoxime. work illustrates how subtle changes design low-spin d6 metal can lead major cellular metabolism novel mechanisms anticancer activity.

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