赫拉
香豆素
细胞凋亡
PI3K/AKT/mTOR通路
丙烯醛
蛋白激酶B
化学
癌细胞
体外
细胞培养
A549电池
细胞毒性
药理学
细胞生长
生物化学
癌症研究
癌症
生物
有机化学
遗传学
催化作用
作者
Lexian Chen,Qianqian Lv,Jianghong Cai,Jiajie Liang,Zhanfeng Liang,Ji Lin,Ying Xiao,Ruiyao Chen,Zhiling Zhang,Yi Hong,Hong Ji
标识
DOI:10.3389/fphar.2023.1141121
摘要
Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e , the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.
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