Two series of novel acridone derivatives were designed and synthesized, with their anticancer activity evaluated. Most of these compounds showed potent antiproliferative activity against cancer cell lines. Among them, compound C4 with dual 1,2,3-triazol moieties exhibited the most potent activity against Hep-G2 cells with IC 50 value determined to be 6.29 ± 0.93 μM. Subsequent experiments showed that C4 could bind to and destabilize Kras gene promoter i-motif structure without significant interaction with its corresponding G-quadruplex. C4 could down-regulate Kras expression in Hep-G2 cells, possibly due to its interaction with the Kras i-motif. Further cellular studies indicated that C4 could induce apoptosis of Hep-G2 cells, possibly related to its effect on mitochondrial dysfunction. These results indicated that C4 could be further developed as a promising anticancer agent.
Home>Syntheses and evaluation of acridone derivatives as anticancer agents targeting Kras promoter i-motif structure
Syntheses and evaluation of acridone derivatives as anticancer agents targeting Kras promoter i-motif structure
- Impact factors: 5.307
- Publication: BIOORGANIC CHEMISTRY
- Author:Zuzhuang Wei, Xiaomin Lin, Siyi Wang, Jiahui Zhang, Dongsheng Ji, Xue Gong, Zhi-Shu Huang, Bing Shu, Ding Li
- DOI citation-doi:10.1016/j.bioorg.2023.106526
- Date:2023-04-07