化学
查尔酮
MAPK/ERK通路
体内
体外
细胞凋亡
细胞生长
癌细胞
A549电池
细胞培养
癌症研究
癌症
生物化学
激酶
立体化学
生物
生物技术
遗传学
作者
Chong Lu,Jian Song,Xinxin Cui,Wenbo Liu,Yin-Ru Li,Guang-Xi Yu,Xinyi Tian,Ya-Feng Wang,Yang Liu,Sai‐Yang Zhang
标识
DOI:10.1016/j.arabjc.2021.103644
摘要
In this work, a series of novel 1,2,4-triazine-chalcone hybrids were designed through the molecular hybridization strategy, synthesized by two step chlorinations and further aldol condensation and evaluated their antiproliferative activity against MGC-803, HCT-116, PC-3, EC-109 and A549 cells. Compound 9l displayed significant antiproliferative activity against MGC-803, HCT-116, PC-3, EC-109 and A549 cell lines with IC50 values of 0.41, 0.43, 0.61, 0.78 and 0.52 μM, respectively. Subsequent mechanistic investigations suggested that compound 9l induced the generation of ROS and inhibited the activation of the ERK pathway. Compound 9l induced extrinsic cell apoptosis by up-regulating DR5 dependent on the generation of ROS, while up-regulation of DR5 caused by compound 9l relied on the inhibition of ERK. Thus, compound 9l inhibited the gastric cancer cells via an axis of ROS-ERK-DR5 in vitro. Compound 9l also showed potent activity on cell proliferation inhibition, and was effective in suppressing the growth of MGC-803 xenograft tumor in nude mice without obvious toxicity. Therefore, compound 9l is to be reported as anti-gastric cancer agent in vitro and in vivo via an axis of ROS-ERK-DR5.
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