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 the methoxy group to the hydroxyl group. 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 IC 50 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.