4.7 Article

Synthesis, anticancer evaluation and mechanism studies of novel indolequinone derivatives of ursolic acid

期刊

BIOORGANIC CHEMISTRY
卷 109, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2021.104705

关键词

Ursolic acid; Indolequinone; Anticancer; PI3K; AKT; mTOR signaling pathway; Apoptosis

资金

  1. National Natural Science Foundation of China [31770616]
  2. Natural Science Foundation for Colleges and Universities in Jiangsu Province [17KJA220002]
  3. Top-notch Academic Programs Project of Jiangsu Higher Education Institutions [PPZY2015C221]

向作者/读者索取更多资源

Novel indolequinone derivatives of ursolic acid bearing ester, hydrazide, or amide moieties were designed, synthesized, and screened for their in vitro antiproliferative activities. Among them, compound 6t exhibited potent activity against three cancer cell lines with low cytotoxicity to normal cells. The compound induced apoptosis in cancer cells and may target the PI3K/AKT/mTOR signaling pathway, suggesting it as a promising lead for novel anticancer agents.
A series of novel indolequinone derivatives of ursolic acid bearing ester, hydrazide, or amide moieties were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (MCF-7, HeLa, and HepG2) and a normal gastric mucosal cell line (Ges-1). A number of compounds showed significant activity against tested cancer cell lines. Among them, compound 6t exhibited the most potent activity against three cancer cell lines with IC50 values of 1.66 ? 0.21, 3.16 ? 0.24, and 10.35 ? 1.63 ?M, respectively, and considerably lower cytotoxicity to Ges-1 cells. Especially, compound 6t could arrest cell cycle at S phase, suppress the migration of MCF-7 cells, elevate intracellular reactive oxygen species (ROS) level, and decrease mitochondrial membrane potential. Western blot analysis showed that compound 6t upregulated Bax, cleaved caspase-3/9, cleaved PARP levels and downregulated Bcl-2 level of MCF-7 cells. All these results indicated that compound 6t could significantly induce the apoptosis of MCF-7 cells. Meanwhile, compound 6t markedly decreased p-AKT and p-mTOR expression, which revealed that compound 6t probably exerted its cytotoxicity through targeting PI3K/AKT/mTOR signaling pathway. Therefore, compound 6t could be a promising lead for the discovery of novel anticancer agents.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据