Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity

Yi-Chen Liu; Ya-Dong Yang; Wen-Qiang Liu; Ting-Ting Du; Ru Wang; Ming Ji; Bei-Bei Yang; Li Li; Xiao-Guang Chen

doi:10.1016/j.bmc.2022.116757

Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity

Bioorg Med Chem. 2022 Jul 1:65:116757. doi: 10.1016/j.bmc.2022.116757. Epub 2022 Apr 21.

Authors

Yi-Chen Liu¹, Ya-Dong Yang¹, Wen-Qiang Liu¹, Ting-Ting Du¹, Ru Wang¹, Ming Ji¹, Bei-Bei Yang¹, Li Li², Xiao-Guang Chen³

Affiliations

¹ Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
² Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: annaleelin@imm.ac.cn.
³ Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: chxg@imm.ac.cn.

PMID: 35504209
DOI: 10.1016/j.bmc.2022.116757

Abstract

Polycyclic aromatic systems have been considered good biological probes, but some may also be good scaffolds for drug development. In this study, a series of benzobis(imidazole) derivatives were identified as STAT3 signal inhibitors, among which compound 24 showed significant inhibition of IL-6 induced JAK/STAT3 signalling pathway activation. Moreover, 24 inhibited cancer cell growth and migration, and induced cell apoptosis as well as cycle arrest in human hepatocellular carcinoma cells (HepG2) and oesophageal carcinoma cells (EC109). Compound 24 also displayed obvious antitumor activity in a mouse HepG2 cell xenograft tumor model without affecting the body weight. These results confirmed that 24 was a potential STAT3 signal inhibitor with certain antitumor activity.

Keywords: Antitumor; Benzobis(imidazole); IL-6/JAK/STAT3 signalling pathway; STAT3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
Humans
Imidazoles
Liver Neoplasms* / pathology
Mice
Mice, Nude
Phosphorylation
STAT3 Transcription Factor / metabolism
Xenograft Model Antitumor Assays

Substances

Imidazoles
STAT3 Transcription Factor
STAT3 protein, human