3019-89-4Relevant articles and documents
Synthesis, pharmacophores, and mechanism study of pyridin-2(1H)-one derivatives as regulators of translation initiation factor 3A
Zhu, Weixing,Shen, Jie,Li, Qianbin,Pei, Qi,Chen, Jun,Chen, Zhuo,Liu, Zhaoqian,Hu, Gaoyun
, p. 654 - 666 (2013/09/24)
Twenty-seven 1,5-disubstituted-pyridin-2(1H)-one derivatives were synthesized and evaluated for their anti-cancer and anti-fibrosis activity by A549 and NIH3T3 cell viability assays, respectively. To study the selectivity between the cancer and fibrosis cell lines, pharmacophore models (F 1-F4) were built in advance for compounds with pyridin-2(1H)-one scaffold, which revealed the relationship between the occupation of the aromatic sub-site F4 and potent anti-cancer activity. The relationship between structure and anti-cancer activity for all target compounds is also reported herein: 1-Phenyl-5-((m-tolylamino)methyl) pyridine-2(1H)-one (22) displayed both potency and selectivity (IC50 = 0.13 mM) toward the A549 cell line through the inhibition of translation initiation, especially by eIF3a suppression, and can be treated as a lead for the design of novel eIF3a regulators and anti-lung cancer agents. A series of pyridin-2(1H)-one derivatives were synthesized. Elucidation of their pharmacophores and mechanism of action suggested that structures with F 4 occupation displayed more selective anti-cancer than anti-fibrosis activity and that they interrupt the initiation phase of translation by acting on the eukaryotic translation initiation factor 3, subunit A.
