<i>In Vivo</i> Selectivity and Localization of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes That Circumvent Platinum Resistance

James P. C. Coverdale, Hannah E. Bridgewater, Ji‐Inn Song, Nichola A. Smith, Nicolas P. E. Barry, Ian Bagley, Peter J. Sadler, Isolda Romero‐Canelón

Journal of Medicinal Chemistry · 2018 · 56 citations · 43 references

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Abstract

(arene = p-cymene, biphenyl, or terphenyl). Their antiproliferative activity does not depend on p21 or p53 status, unlike cisplatin, and their selective potency toward cancer cells involves the generation of reactive oxygen species. Evidence of such a mechanism of action has been found both in vitro and in vivo. This work appears to provide the first study of osmium complexes in the zebrafish model, which has been shown to closely model toxicity in humans. A fluorescent osmium complex, derived from a lead compound, was employed to confirm internalization of the complex, visualize in vivo distribution, and confirm colocalization with reactive oxygen species generated in zebrafish.

References

43