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