Regulating p53/PUMA pathway on Cervical Cancer C-33A and HeLa cells of Acanthus ilicifolius Linn alkaloid 2-Benzoxazolinone Derivatives

The purpose of this study is to investigate the targeted activation effect of p53 on Acanthus ilicifolius Linn alkaloid 2-benzoxazolinone derivatives in cervical cancer C-33A and HeLa cells, and to explore its mechanism of action. A one-pot method was used to synthesize Acanthus ilicifolius Linn alkaloid 2-benzoxazoline derivatives by Ugi 4-component coupling/halogenation cyclization reaction. The effect of the drug on the proliferation of C-33A and HeLa cells was detected by CCK-8 assay, the effect of the drug on cell migration was detected by Transwell assay, and cell apoptosis was detected by Hoechst PI staining. Through molecular docking, we predict that the derivatives of the alkaloid 2-benzoxazolinone have the potential to stably bind the p53-Y220C, which points out the direction for us to optimize the structures of these derivatives of the alkaloid 2-benzoxazolinone later. The RT-qPCR results showed a significant increase in p53 gene expression level and PUMA gene expression level, indicating that the alkaloid 2-benzoxazolinone derivative BOABB may have anticancer effects on cervical cancer by up-regulating p53/PUMA pathway.