Efficient Palladium-Triggered Release of Vorinostat from a Bioorthogonal Precursor

Bioorthogonal
uncaging strategies have recently emerged as an experimental therapeutic
approach to control drug release. Herein we report a novel masking
strategy that enables to modulate the metal chelating properties of
hydroxamic acid groups by bioorthogonal chemistry using Pd-functionalized
resins. This novel approach allowed to devise an inactive precursor
of the histone deacetylase inhibitor vorinostat that was efficiently
uncaged by heterogeneous Pd catalysis in cell culture models of glioma
and lung cancer.