Year: 2025
Type: article
Abstract: Disulfiram (DSF), a well-known anti-alcoholism drug, exhibits potent anticancer activity via its metabolite, diethyldithiocarbamate (DDC), which forms a cytotoxic copper complex that selectively targets cancer stem cells. However, its clinical utility is limited by poor solubility and rapid plasma metabolism. This study explores saccharide-linked DDCs as novel prodrugs designed to enhance stability, solubility, and tumour-selective activation. These compounds feature thioglycosidic bonds that shield the DDC moiety from premature degradation while retaining its metal-chelating function to form the active copper(II)bis(N,N-diethyldithiocarbamate) (Cu(DDC)2) complex. The synthesised derivatives were characterised and evaluated for serum stability and in vitro cytotoxicity across several cancer cell lines, including colorectal, breast, lung, and brain cancers. Copper-complexed saccharide-DDC prodrugs demonstrated remarkable cytotoxicity, with improved biostability and solubility profiles. These findings highlight the potential of saccharide-linked DDCs as stable, copper-activated prodrugs for cancer therapy. Further in vivo studies are warranted to validate their pharmacokinetics and clinical relevance.
DOI: 10.3390/ijms26125589
Authors: Mohammad Najlah, Niamh McCallum, Ana Maria Pereira, Dan Alves, Niusha Ansari-Fard, Sahrish Rehmani, Ayşe Kaya
Institution: Anglia Ruskin University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4411212021