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.

中文翻译：

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4H-噻吩并[3,2-b]吡咯衍生物作为潜在抗癌剂的发现

在这项研究中，我们描述了 4 H-噻吩并[3,2- b ]吡咯衍生物的发现，该衍生物是一种有用的支架，可用于获得治疗结肠癌的有效先导化合物。我们首先从来自化合物库筛选的 4 H-噻吩并[3,2- b ]吡咯衍生物开始，然后根据细胞活性和药效团模型优化它们的结构。细胞生长抑制率测定表明，该系列化合物对结肠癌细胞的抑制活性优于其他受试肿瘤细胞。此外，最活跃的化合物8i的目标通过目标捕捞策略进行探索，并通过分子对接和生物活性分析进行验证。细胞凋亡和流式细胞术结果表明，化合物8i可能通过抑制蛋氨酸氨肽酶2的活性诱导细胞凋亡，因此化合物8i可能是蛋氨酸氨肽酶2的有效抑制剂。