In this work, a series of novel benzimidazole derivatives were designed and synthesized as Pin1 inhibitors. Protease-coupled assay was used to investigate the Pin1 inhibitory potency of all synthesized compounds. Thirteen of them showed preferable Pin1 inhibitory effects with IC50 values lower than 5 μM, and 12a, 15b, 15d and 16c exhibited the most promising Pin1 inhibitory activity at low micromolar level (0.33-1.00 μM) than the positive control compound Juglone. Flow cytometry results showed that treating PC-3 cells with 16c caused slight cycle arrest in a concentration-dependent manner. The structure-activity relationships of R1, R2, R3 and linker of the benzimidazole derivatives were analyzed in detail, which would help further exploration of new Pin1 inhibitors.
Keywords: 4-(1H-benzoimidazol-2-yl)-benzsulfamides; PC-3; PPIase; Pin1 inhibitors; Prostate cancer.
Copyright © 2018. Published by Elsevier Ltd.