Thiol-Reactive Arylsulfonate Masks for Phenolate Donors in Antiproliferative Iron Prochelators.

ABSTRACT: Tridentate thiosemicarbazones, among several families of iron chelators, have shown promising results in anticancer drug discovery because they target the increased need for iron that characterizes malignant cells. Prochelation strategies, in which the chelator is released under specific conditions, have the potential to avoid off-target metal binding (for instance, in the bloodstream) and minimize unwanted side effects. We report a prochelation approach that employs arylsulfonate esters to mask the phenolate donor of salicylaldehyde-based chelators. The new prochelators liberate a tridentate thiosemicarbazone intracellularly upon reaction with abundant nucleophile glutathione (GSH). A 5-bromo-substituted salicylaldehyde thiosemicarbazone (STC4) was selected for the chelator unit because o

SUBMITTER: Wu W 

PROVIDER: S-EPMC10188280 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature