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

Abstract

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.

Design, in silico studies, synthesis, and in vitro anticancer assessment of new naphthylidene isoxazolidinedione derivatives

“…[16][17][18][19][20][21][22][23][24][25] Interestingly, there are countless pieces of literature demonstrating compounds with anticancer activity incorporating various heterocyclic rings. 17,19,[25][26][27][28][29][30] On a similar path, we have recently reported new small molecules incorporating heterocyclic rings, imidazolidinedione, and pyrrolidinedione showing excellent antitumor activity. 19,26 Therefore, with our previous experience and knowledge, by considering the structural modification of our previously reported analogs, we developed compounds incorporating the TZD bio-isostere which is a heterocyclic ring isoxazolidinedione, to evaluate the effect of this bio-isosteric replacement over the anticancer activity of these compounds (Figure 2).…”

“…However, we also published compounds without the TZD nucleus showing good antiproliferative activity (Figure 1). 16–25 Interestingly, there are countless pieces of literature demonstrating compounds with anticancer activity incorporating various heterocyclic rings 17,19,25–30 . On a similar path, we have recently reported new small molecules incorporating heterocyclic rings, imidazolidinedione, and pyrrolidinedione showing excellent antitumor activity 19,26 .…”

Pyrrole: A Decisive Scaffold for the Development of Therapeutic Agents and Structure‐Activity Relationship

“…According to the scientific results, the chemical caused the apoptosis of the colon cancer cells HCT116 and HT29. [193] Compound 101 shows promising activity against gastrointestinal stromal tumours against the cell line GIST T-1 with the IC 50 value of 2.55 � 0.11 μM. Notably, the compound's action was concentration-dependent and perceptible against GIST tumor cells that were both IM-sensitive and IM-resistant.…”

“…Molecular docking confirmed this conclusion. According to the scientific results, the chemical caused the apoptosis of the colon cancer cells HCT116 and HT29 [193] . Compound 101 shows promising activity against gastrointestinal stromal tumours against the cell line GIST T‐1 with the IC 50 value of 2.55±0.11 μM.…”