Polydatin as a Mixed‐Type Inhibitor of CYP1B1: An Integrative Study Combining Enzymatic Assays and Molecular Simulations

ABSTRACT

Cytochrome P450 1B1 (CYP1B1) is often upregulated in tumor tissues, whereas its expression in many normal tissues is relatively low. This expression pattern makes CYP1B1 a possible enzymatic target in cancer‐related studies. Polydatin possesses multiple pharmacological activities. In this work, the inhibitory activity of polydatin against CYP1B1 was first examined by enzyme assay. Molecular docking and molecular dynamics simulation were used to analyze the possible binding mode, and ADMET prediction was used to assess its basic drug‐like properties. Polydatin inhibited CYP1B1 activity with an IC ₅₀ value of 0.11 ± 0.01 μM. Kinetic analyses indicated a mixed‐type inhibition pattern. Molecular dynamics simulations further supported the stability of the CYP1B1‐polydatin complex. ADMET analysis suggested acceptable drug‐likeness and a relatively low risk of major CYP‐mediated drug‐drug interactions. These research results provide a basis for conducting further pharmacological evaluations of polydatin.