Design, synthesis, and biological evaluation of bergapten derivatives as potent anti-pancreatic cancer agents

Bergapten, a natural product from <i>Zanthoxylum bungeanum</i> Maxim., exhibits anticancer, antibacterial, anti-inflammatory, and hypolipidemic effects. A derivative, FSG-Y5 showed potent activity against pancreatic cancer cells PANC-1 (IC₅₀ = 2.31 ± 0.25 µM) and CFPAC-1 (IC₅₀ = 4.41 ± 0.47 µM), inhibiting their survival, migration, and invasion while inducing apoptosis <i>via</i> Bax and Cleaved caspase-3 regulation. FSG-Y5 also suppressed pancreatic cancer organoids and zebrafish tumor growth in a concentration and time-dependent manner. These findings highlight bergapten derivatives as promising anticancer candidates, with FSG-Y5 as a potential anti-pancreatic cancer agent for further study.