largazole and isobutylene

Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer. Described herein is a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide, and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, it is shown that the activity of histone deacetylase inhibitor largazole can be switched off when stapled, but selectively switched on within cancer cells when irradiated with non-phototoxic light.

Topics: Alkenes; Cell Survival; Depsipeptides; Dose-Response Relationship, Drug; Free Radicals; HCT116 Cells; Histone Deacetylase Inhibitors; Humans; Molecular Structure; Photochemical Processes; Structure-Activity Relationship; Sulfhydryl Compounds; Thiazoles; Ultraviolet Rays