Synthesis, biological evaluation, network pharmacology, and molecular docking of benzophenone as antitumor agents

Using Eaton's reagent or boron trifluoride ether, 24 compounds were synthesized in a 1- or 2-step reaction, with the conversion of methoxy and hydroxyl groups. Next, the in vitro antitumor activity of all compounds and the antioxidant activity of compounds 1 to 3 were investigated. Compounds 7, 13, 15, 17, 18, 20, 22, and 24 exhibited strong antitumor activity and were considered promising compounds. Among them, compounds 7, 13, and 18 exhibited very strong inhibitory activity against HL-60 cells with IC50 values of 0.55, 0.29, and 0.72 μM, respectively. Furthermore, compounds 1 to 3 exhibited moderate antioxidant activity and their mechanism of action was further validated by computational chemistry. Finally, the antitumor mechanism of the above 8 compounds was investigated through network pharmacology and molecular docking, and 19 key genes and 20 pathways were obtained. These results will allow future development of benzophenone and its derivatives.