Syntheses, crystal structures of copper (II)-based complexes of sulfonamide derivatives and their anticancer effects through the synergistic effect of anti-angiogenesis, anti-inflammation, pro-apoptosis and cuproptosis.

Three novel copper(II)-based complexes Cu-1, Cu-2, and Cu-3 containing sulfamethoxazole or sulfamethazine ligand were obtained, and their single structures were characterized. Both Cu-1 and Cu-3 show a broad spectrum of cytotoxicity than Cu-2, and Cu-1 is more cytotoxic than Cu-3. What's interesting is that Cu-1 can exhibit obvious inhibitory effect on the growth of human triple-negative breast cancer in vivo and vitro through anti-proliferative, anti-angiogenic, anti-inflammatory, pro-apoptotic and cuproptotic synergistic effects. Though Cu-3 shows no significant cytotoxicity against MDA-MB-231 cells, it can significantly inhibit the growth of SKOV3 cells in vitro by down-regulating the expression of some key proteins in the VEGF/VEGFR2 signaling pathway and the expression of some pro-inflammatory cytokines, and by disrupting the balance of intracellular reactive oxygen species levels.