Year: 2026
Type: article
Abstract: Cuprotosis is a unique mode of cell death being explored in many new therapeutic anticancer studies. A widely used approach is the combination of Cu(II) salts with diethyldithiocarbamate disulfide, disulfiram (DSF), also known as the alcohol‐sensitizing drug Antabuse, which generates the toxic Cu(II)bis(diethyldithiocarbamate), Cu(DTC) 2 , in a complex redox reaction. The mechanism for the generation of Cu(DTC) 2 in this reaction, which we term the DSF/Cu reaction, has been examined using high‐resolution liquid chromatography‐mass spectroscopy (HR LCMS) by monitoring the reaction at different sampling times to determine sequential speciation of reaction intermediates. Other intermediates of this reaction are characterized by the addition of adduct‐forming “traps” used to characterize thiol and sulfenic acid species generated throughout the reaction. The time‐resolved spectra reveal that one initial reaction is a 2‐electron oxidation of a thione moiety in DSF to a sulfine (DSF‐O), which implies a concurrent reduction of Cu(II) to Cu(0). Other results suggest the involvement of Cu(I) in the titled reaction, most likely formed by comproportionation of Cu(0) with Cu(II) in the MeCN/H 2 O solutions used. Additional intermediate products indicate a variety of sulfur oxidation, hydrolysis, and insertion/extrusion reactions forming species that also feed into pathways generating Cu(DTC) 2 .
Source: ChemBioChem
DOI: 10.1002/cbic.70562
Authors: Jordan Lyons, Patrick J. Farmer
Institution: Baylor University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,430
Funder: Baylor University
OpenAlex ID: W7222994072