Bischalcone derivatives with fluorine and methoxy functional groups: Synthesis, molecular docking, and biological evaluation as potential anticancer agents

•New bischalcone derivatives were synthesized and fully characterized by various spectroscopic techniques.•An evaluation was conducted to determine the efficacy of all synthesized compounds on head and neck cancer.•Computational studies were conducted to comprehend the process by which the compounds exert their effects. The present study employed the Claisen-Schmidt condensation reaction to synthesize a series of bischalcones featuring fluorine atoms positioned at different positions in the B rings and 1,3,5-trimethoxy groups in the A ring. The impact of these bischalcones on head and neck cancer cells was assessed through in vitro and in silico methodologies. As determined by the cell viability assay, compound 20, which had an IC50 value of 6.5 ± 0.2 μM, was the most lethal to FaDu cells of all compounds, although its cytotoxicity against healthy PNT1a cells was relatively low. Molecular docking and molecular dynamics simulations were performed on five receptors identified through in silico biological activity analysis: EGFR, Pim-1 kinase, PI3Kα/mTOR, VEGFR, and P2Y1 Purinergic receptor. The compounds exhibited a primary target of EGFR, as evidenced by their effectiveness that was approximately one hundred times greater than that of the reference molecule. Compounds 18 and 20 exhibited remarkable efficacies as precursors to anticancer drugs. [Display omitted]