Design, Synthesis And Bioactivities Evaluation In Vitro Of N-(5-formyl-2-(4-methylpiperazin-1-yl)Phenyl)Amide Compounds

Over-activation or over-expression of p-catenin could induce tumorigenesis. Interaction of (3-catenin with TCF is a key step in the activation of the proliferative genes in response to upstream signals of this Wnt/β-catenin pathway. Therefore,β-catenin could become an important protein for designing small molecule inhibitors of Wnt/β-catenin signaling pathway.In this thesis, according to β-catenin crystal structure, virtual screening was performed from Mybridge and Specs database, and the four best small molecule compounds were firstly selected. Based on the four compounds, two kinds of derivatives of benzimidazole and N-(5-fonnyl-2-(4-methylpiperazin-l-yl)phenyl)amide compounds were designed, respectively, through molecular docking. Ten N-(5-formyl-2-(4-methylpiperazin-1-yl)phenyl)amide compounds Q1-Q10were further selected and synthesized, and their structures were confirmed by IR, MS,’H NMR,13C NMR and HRMS, respectively. The antiproliferative effect of the synthesized compounds were also evaluated on human colon cancer cell lines SW480, uterine cervical cancer cell lines HeLa, non small cell lung cancer cell lines A549and cecum cancer cell lines HCT-8by MTT assay. And four compounds Ql, Q4, Q8and Q9exhibited obvious inhibitory activity. In addition, immune activity and Wnt signaling pathway of the compounds were preliminary studied. The results cound support further development of design idea for Wnt/β-catenin signaling pathway small molecular inhibitors.