In Vivo Selectivity and Localization
of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes
That Circumvent Platinum Resistance
Version 2 2018-10-19, 20:48
Version 1 2018-10-05, 14:22
Posted on 2018-10-19 - 20:48
Platinum
drugs are widely used for cancer treatment. Other precious
metals are promising, but their clinical progress depends on achieving
different mechanisms of action to overcome Pt-resistance. Here, we
evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts
[(η6-arene)Os(N,N′)], and 18-electron phenylazopyridine complexes [(η6-arene)Os(N,N’)Cl/I]+ (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.
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Coverdale, James
P. C.; Bridgewater, Hannah E.; Song, Ji-Inn; Smith, Nichola A.; P. E. Barry, Nicolas; Bagley, Ian; et al. (2018). In Vivo Selectivity and Localization
of Reactive Oxygen Species (ROS) Induction by Osmium Anticancer Complexes
That Circumvent Platinum Resistance. ACS Publications. Collection. https://doi.org/10.1021/acs.jmedchem.8b00958
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AUTHORS (8)
JC
James
P. C. Coverdale
HB
Hannah E. Bridgewater
JS
Ji-Inn Song
NS
Nichola A. Smith
NP
Nicolas P. E. Barry
IB
Ian Bagley
PS
Peter J. Sadler
IR
Isolda Romero-Canelón
KEYWORDS
Osmium Anticancer ComplexesReactive Oxygen Specieselectronantiproliferative activitycancer cellsROSarenereactive oxygen specieszebrafish model13 organo-Os complexesp 53 statusosmium complexesVivo SelectivityCircumvent Platinum Resistance Platinum drugsp 21model toxicitymechanismcancer treatmentvivo distribution