PtIV prodrugs can overcome resistance and side effects of conventional PtII anticancer therapies. By 19 F-labeling of a PtIV prodrug (Pt-FBA, FBA=p-fluorobenzoate), the activation under physiological conditions could be investigated. Unlike single-electron reductants, multi-electron agents can efficiently promote the two electrons reduction of PtIV to PtII . The activation of Pt-FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to E. coli, Pt-FBA is reduced intracellularly and free FBA can shuttle out of the cell. The reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of ZnII ions. When injected into mice, Pt-FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt-FBA can accumulate to detectable levels in liver and kidneys. The 19 F NMR approach has the advantage of avoiding the interference of all background signals.

19 F NMR Allows the Investigation of the Fate of Platinum(IV) Prodrugs in Physiological Conditions

Fabio Arnesano;Giovanni Natile
;
2022

Abstract

PtIV prodrugs can overcome resistance and side effects of conventional PtII anticancer therapies. By 19 F-labeling of a PtIV prodrug (Pt-FBA, FBA=p-fluorobenzoate), the activation under physiological conditions could be investigated. Unlike single-electron reductants, multi-electron agents can efficiently promote the two electrons reduction of PtIV to PtII . The activation of Pt-FBA in cell lysate is highly dependent upon the type of cancer cells. When administered to E. coli, Pt-FBA is reduced intracellularly and free FBA can shuttle out of the cell. The reduction rate greatly increases by inducing metallothionein overexpression and is lowered by addition of ZnII ions. When injected into mice, Pt-FBA undergoes fast reduction in the bloodstream accompanied by metabolic degradation of FBA; nevertheless, unreduced Pt-FBA can accumulate to detectable levels in liver and kidneys. The 19 F NMR approach has the advantage of avoiding the interference of all background signals.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/377791
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