Identification of novel STAT3 inhibitors bearing 2-acetyl-7-phenylamino benzofuran scaffold for antitumour study

[Display omitted] Signal transducer and activator of transcription 3 (STAT3) is identified as a promising target for multiple cancer therapy and attracts widespread concern. Herein, we reported the discovery of a series of 2-acetyl-7-phenylamino benzofuran derivatives as STAT3 inhibitors using scaff...

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Published in:Bioorganic & medicinal chemistry 2020-12, Vol.28 (24), p.115822-115822, Article 115822
Main Authors: Wang, Feng, Feng, Kai-Rui, Zhao, Jia-Ying, Zhang, Jian-Wei, Shi, Xin-Wei, Zhou, Jian, Gao, Dingding, Lin, Guo-Qiang, Tian, Ping
Format: Article
Language:English
Subjects:
2-Acetyl-7-phenylamino benzofurans
Antitumor study
Molecular docking
STAT3 inhibitors
Structure-activity relationships
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Summary:[Display omitted] Signal transducer and activator of transcription 3 (STAT3) is identified as a promising target for multiple cancer therapy and attracts widespread concern. Herein, we reported the discovery of a series of 2-acetyl-7-phenylamino benzofuran derivatives as STAT3 inhibitors using scaffold fusion strategy. Further structure activity relationship study led to the discovery of compound C6, which displayed the most potent anti-proliferation activities against MDA-MB-468 cells (IC50 = 0.16 μM). Western blot assay demonstrated that C6 inhibited the activation of STAT3 (Tyr705) without influencing the phosphorylation of STAT1 (Tyr701). Further mechanistic studies indicated that C6 caused a notable G2/M cycle-arresting and early apoptosis in a concentration-dependent manner in MDA-MB-468 cells. Finally, molecular modelling study elucidated the binding mode of C6 in STAT3 SH2 domain.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2020.115822