Synthesis of Salidroside Derivatives at C4 Position of Benzene Ring and Its Effect on Hep3B Cell Viability

Salidroside has been reported to have various pharmacological activities, including hypoxia tolerance, anti-radiation, and antitumor. In this study, we studied the antitumor activity of salidroside ether derivatives in the human hepatocellular carcinoma cell line Hep3B. We created eleven new benzyl halide derivatives called S1-S11 by modifying the phenolic hydroxyl groups at the C4 position of salidroside. The compounds were shown to inhibit tumor proliferation in the in vitro CCK-8 assay. Compounds S4, S5, S6, S7, S8, and S11 demonstrated strong inhibitory activity anti-human hepatic cancer cell Hep3B, with IC₅₀ values of 67.89, 97.55, 73.67, 57.92, 88.29, and 33.39 μM, respectively. Under the inverted microscope, compared with the blank group, after 48 h of administration, it showed obvious proliferation inhibition and apoptosis characteristics. In addition, network pharmacology predicts that these derivatives may have the effect of regulating the nervous system and protecting neuronal cells without violating Lipinski's Rule. In summary, the benzyl halide modification on the C4 phenolic hydroxyl group on the benzene ring of SAL can improve its antitumor activity, which provides ideas for the subsequent development of salidroside antitumor drugs.