Journal of Medicinal Chemistry · 2018 · 56 citations · 43 references
MedicineOncologyPharmacologyCancer PharmacologyChemotherapyMolecular OncologyBioinorganic ChemistryCoordination ChemistryReactive Oxygen SpeciesAntiproliferative AgentsAntiproliferative Drug ActionMetalloid ComplexesOrganometallic Anticancer AgentsP53 InactivationPlatinum CompoundsPlatinum-based AgentsReactive Oxygen Species Generation
(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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