| Summary: | Peptidyl-prolyl <i>cis/trans</i> isomerase Pin1 plays a key role in amplifying and translating multiple oncogenic signaling pathways during oncogenesis. The blockade of Pin1 provided a unique way of disrupting multiple oncogenic pathways and inducing apoptosis. Aiming to develop potent Pin1 inhibitors, a series of benzimidazole derivatives were designed and synthesized. Among the derivatives, compounds <b>6h</b> and <b>13g</b> showed the most potent Pin1 inhibitory activity with IC<sub>50</sub> values of 0.64 and 0.37 μM, respectively. In vitro antiproliferative assay demonstrated that compounds <b>6d</b>, <b>6g</b>, <b>6h</b>, <b>6n</b>, <b>6o</b> and <b>7c</b> exhibited moderate antiproliferative activity against human prostate cancer PC-3 cells. Taken together, these unique benzimidazole derivatives exhibited great potential to be further explored as potent Pin1 inhibitors with improved potency.
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