Investigation of the Inhibitory Effects and Underlying Mechanisms of Vitexin Derivatives Targeting CDK1 in HCT Colorectal Cancer Cells.

This study designs and synthesizes a series of vitexin derivatives to evaluate their inhibitory activity against human colon cancer HCT-116 cells and to explore the underlying mechanisms. Antiproliferative effects are assessed using the CCK-8 assay. Molecular docking with Schrödinger software and molecular dynamics simulations analyze interactions between candidate compounds and CDK1. Cell cycle distribution is determined by flow cytometry, while western blotting, immunofluorescence, and CDK inhibition assays evaluate CDK1/cyclin B expression. Most derivatives show stronger inhibitory activity than the parent compound. Vitexin exhibits an IC₅₀ of 210.23 ± 40.89 μM, whereas Butylated vitexin (M3) displays markedly enhanced potency (IC₅₀ = 8.73 ± 1.40 μM) and induces G₂/M phase arrest. Molecular docking reveals strong binding affinity between M3 and CDK1 (Docking score -10.127), and molecular dynamics simulations confirm the stability of the M3-CDK1 complex with inhibitory effects comparable to flavopiridol (FP). Furthermore, M3 downregulates CDK1/cyclin B expression in HCT-116 cells (IC₅₀ = 9.83 ± 2.65 μM). M3 may suppress HCT-116 cell proliferation by targeting CDK1/cyclin B and inducing G₂/M phase arrest.