Sulphonamide derivatives with a triazine core as novel inducers of apoptosis and pyroptosis in glioblastoma multiforme cells

Glioblastoma multiforme (GBM) is a highly aggressive brain tumour with few effective treatment options. This study evaluated two novel triazine-based sulphonamides, MM118 and MM119, for their anticancer effects on GBM cells. <i>In vitro</i> cell viability assays showed that both compounds were highly potent, killing GBM cells at low-micromolar concentrations. They induced apoptosis in cancer cells, evidenced by Annexin V/PI staining and caspase-3/7 activation. Both the intrinsic and extrinsic apoptosis pathways were engaged, as shown by mitochondrial depolarisation along with caspase-9 and caspase-8 activation. The compounds also increased reactive oxygen species levels, further promoting apoptosis. Notably, MM118 and MM119 triggered pyroptosis - an inflammatory form of cell death - indicated by caspase-1 activation and NF-κB translocation. In a zebrafish xenograft model, both compounds significantly reduced tumour growth. These findings highlight MM118 and MM119 as promising candidates for GBM therapy that may overcome resistance by engaging multiple cell-death pathways.