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

Journal Name: Letters in Drug Design & Discovery

Volume 11 , Issue 6 , 2014

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Graphical 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.

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Article Details

Year: 2014
Page: [762 - 769]
Pages: 8
DOI: 10.2174/1570180811666140116214111
Price: $65

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