铅化合物
化学
细胞凋亡
A549电池
酶
细胞周期检查点
组合化学
醋酸
立体化学
细胞周期
生物化学
体外
作者
Simone Di Micco,Stefania Terracciano,Dafne Ruggiero,Marianna Potenza,Maria Carmela Vaccaro,Katrin Fischer,Oliver Werz,Ines Bruno,Giuseppe Bifulco
标识
DOI:10.3389/fchem.2021.676631
摘要
We report the implementation of our in silico /synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC 50 values on A549 cell lines compared to CAY10526, selected as reference compound. The most promising compound 2c induced the cycle arrest in the G 0 /G 1 phase at 24 h of exposure, whereas at 48 and 72 h, it caused an increase of subG 0 /G 1 fraction, suggesting an apoptosis/necrosis effect.
科研通智能强力驱动
Strongly Powered by AbleSci AI