Novel synthesis naringenin-benzyl piperazine derivatives prevent glioblastoma invasion by inhibiting the hypoxia-induced IL6/JAK2/STAT3 axis and activating caspase-dependent apoptosis

•A series of N-benzyl piperazine derivatives of naringenin (8 compounds) were synthesized.•The anti-proliferative effect of all eight synthesized compounds was determined in GBM cells.•Two compounds with low IC50 values were selected for molecular studies to determine their mechanisms of action.•The anti-invasion effects of two selected compounds on GBM tumor spheroids were investigated using hypoxia, JAK/STAT, and apoptosis signaling pathways.•NDs exert a strong anti-invasion effect via inhibiting the hypoxia-induced IL6/JAK2/STAT3 axis and inducing caspase-dependent mitochondrial apoptosis.