Synthesis of a Novel Hemicucurbituril and Its Inhibitory Activity of Cathepsin L

A novel hemicucurbituril was designed and synthesized, and its inhibition activity against cathepsin L was evaluated. A molecular docking method was used to verify the activity and the cytotoxicity of the compound investigated using an MTT assay. Our results showed that the compound possessed good inhibitory activity against cathepsin L. At a concentration of 0.2 mg/mL, the inhibitory rate against cathepsin L was 58.09% and its IC₅₀ value was 20.63 μM. Molecular docking indicates that the hydrogen atoms on the phenolic hydroxyl groups on both sides of the hemicucurbituril formed hydrogen bonding interactions with the Asp-114 and Ser-213 amino acid residues on cathepsin L, respectively, which can effectively bind to the active site of cathepsin L and inhibit the biological function of the target enzyme. In addition, the hemicucurbituril has low in vitro toxicity toward HepG2, HK-2, and H9C2, and can be used as an inhibitor of cathepsin L, a potential coronavirus drug target.