New paper in European Journal of Medicinal Chemistry

Check out our new paper in the journal European Journal of Medicinal Chemistry. The interdisciplinary article is coauthored by researchers from the University of Warsaw (Wojciech Witkowski, Michał Żebrowski, Martyna Boruc, Piotr Łętowski, and Grzegorz Litwinienko), who worked in close collaboration with research group headed by Maciej Wnuk and Anna Lewińska from the University of Rzeszów.

The thiocarbonyl analog of chrysin induces apoptosis and oxidative stress-mediated unfolded protein response in breast cancer cells
European Journal of Medicinal Chemistry, 2026, 318, 119201, DOI: 10.1016/j.ejmech.2026.119201

The study investigated the synthesis and biological activity of thiochrysin and thiobaicalein, new thiocarbonyl analogs designed to improve the limited bioavailability and anticancer efficacy of natural flavones. The researchers successfully identified thiochrysin as a potent agent that, at a low concentration of 1 μM, significantly sensitizes ER-positive (MCF-7) and HER2-positive (SK-BR-3) breast cancer cells to apoptotic death compared to the unmodified parent flavone.  The main success of the research lies in characterizing the mechanism: thiochrysin triggers lethal oxidative stress through elevated superoxide production, which in turn activates the unfolded protein response (UPR) signaling pathways (specifically IRE1 and ATF6) and the ER-associated chaperone GRP78.  Furthermore, thiochrysin demonstrated high efficacy in 3D breast cancer spheroid models and was found to be effective against doxorubicin-induced senescent and drug-resistant breast cancer cells.  These findings suggest that C4 thionation is a promising strategy for designing more effective flavone-based therapies to overcome drug resistance in breast cancer.