Radical‐Mediated Thiol‐Ene Strategy: Photoactivation of Thiol‐Containing Drugs in Cancer Cells

Abstract

Photoactivated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases such as cancer.D escribed herein is aphotoactivation decaging method of isobutylene-caged thiols through aU V-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine,c yclic disulfide-peptide,a nd thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and aphotoinitiator.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 nonphototoxic light.

Cyanine‐ and Rhodamine‐Derived Alkynes for the Selective Targeting of Cancerous Mitochondria through Radical Thiol‐Yne Coupling in Live Cells

“…Only under cell‐free conditions, a radical carbohydrate‐alkyne conjugation to bioavailable thiols has so far been reported by Dondoni, [22] which nevertheless nicely underlines the bio‐orthogonality of the reaction type [22–23] . The assumption that poor reaction control may have been a key issue in preventing applications of radical thiol‐yne chemistry in living cells is also supported by successful examples of thiol‐ene reactions, [24] which are less prone to side‐product formation.…”