Discovery of 4H-thieno[3,2-b]pyrrole derivatives as potential anticancer agents

In this study, we describe the discovery of the 4H-thieno[3,2-b]pyrrole derivatives as an useful scaffold to obtain potent lead compounds for the treatment of colon cancer. We first started with the 4H-thieno[3,2-b]pyrrole derivatives which come from compound libraries screening, and then optimized their structures based on the cellular activities and pharmacophore models. The inhibition rate of cell growth assay demonstrated that this series compounds showed better inhibitory activities against colon cancer cells than other tested tumor cells. Moreover, the target of the most active compound 8i was explored by target fishing strategy and validated by molecular docking and biological activity analysis. The results of apoptosis and flow cytometry demonstrated that compound 8i induces cell apoptosis probably by inhibiting activity of methionine aminopeptidase 2, therefore compound 8i may be a potent inhibitor to methionine aminopeptidase 2.

Automated summary

The study found a new compound scaffold with potential therapeutic effects on colon cancer, which was optimized based on cellular activity and pharmacophore models. The compounds demonstrated excellent inhibitory activity against colon cancer cells, with the most active compound inducing cell apoptosis by inhibiting a specific enzyme activity.