设计并合成了两个系列的新型丙烯酮衍生物，评估了它们的抗癌活性。这些化合物中大多数对癌细胞系表现出强烈的抗增殖活性。其中，双重1,2,3-三唑基团的化合物C4对Hep-G2细胞表现出最强的活性，IC50值为6.29±0.93 μM。随后的实验表明，C4能够结合并破坏Kras基因启动子i-结构，而不与其对应的G-四链体发生显著的相互作用。C4能够下调Hep-G2细胞中Kras的表达，可能是由于其与Kras i-结构的相互作用。进一步的细胞研究表明，C4能够诱导Hep-G2细胞凋亡，可能与其对线粒体功能的影响有关。这些结果表明，C4可以进一步开发为一种有前途的抗癌药物。 版权所有 © 2023 Elsevier Inc.。

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 IC50 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.Copyright © 2023 Elsevier Inc. All rights reserved.