Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

Back

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

Author(s): Chunqi Hu, Jianfeng Shen, Kejun Bian, Ruoyu Zhang, Liping Deng.

Graphical Abstract:


Abstract:

A series of N1-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 G2/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.

Keywords: 2, 4, 5-triphenyl imidazole, Anti-cancer, p53-MDM2 binding, Heterocyclic compounds.

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 11
ISSUE: 6
Year: 2014
Page: [762 - 769]
Pages: 8
DOI: 10.2174/1570180811666140116214111
Price: $58