文献类型：期刊文献

英文题名：Design, Synthesis and Biological Evaluation of 2,4,5-Triphenylimidazole Derivatives with Preliminary SAR

作者：Hu, Chunqi[1];Shen, Jianfeng[2];Bian, Kejun[1];Zhang, Ruoyu[3];Deng, Liping[1]

机构：[1]Shaoxing Univ, Dept Chem & Chem Engn, Shaoxing 312000, Peoples R China;[2]Zhejiang Zhenyuan Pharmaceut, Shaoxing 312000, Zhejiang, Peoples R China;[3]Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Geriatr, Hangzhou 310009, Zhejiang, Peoples R China

年份：2014

卷号：11

期号：6

起止页码：762

外文期刊名：LETTERS IN DRUG DESIGN & DISCOVERY

收录：SCI-EXPANDED(收录号：WOS:000337105100009)、、Scopus(收录号：2-s2.0-84902457341)、WOS

基金：This project is funded by the Natural Science Foundation of Zhejiang Province, China (LQ13H300001 and Y2100872), and supported by the National Science Foundation for Young Scholars of China (No. 81202411). The authors also thank Dr. Shaomeng Wang from University of Michigan for providing the plasmid of MDM2 1-118) and the tracer, and Dr. Jia Li from the National Center for Drug Screening for helping on the protein purification experiment.

语种：英文

外文关键词：2, 4, 5-triphenyl imidazole; Anti-cancer; p53-MDM2 binding; Heterocyclic compounds

外文摘要：A series of N-1-substituted 2,4,5-triphenyl imidazole derivatives was designed, synthesized and evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferative activities in vitro against four human cancer cell lines (PC3, KB, A549 and HCT116). Although logical evaluation revealed weak p53-MDM2 binding inhibitory activities, most of the obtained molecules displayed moderate to potent cytotoxicities against tested cell lines. As a potential lead compound for further optimization, compound 9c was evaluated as the most potent compound against four cell lines and could induce cell cycle arrest at G(2)/M phase. The binding mode of compound 9f and MDM2 was further studied by docking analysis and the unexpected interaction mode revealed that this series of compounds may take part into a different binding modes as the lead compound Such as Nutlin, which could induce a different mechanism in cancer therapy.