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.
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.
Bioorg Med Chem. 2022 Jul 1;65:116757. doi: 10.1016/j.bmc.2022.116757. Epub 2022 Apr 21.
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.
多环芳烃系统已被认为是良好的生物探针，但有些也可能是药物开发的良好支架。在这项研究中，一系列苯并（咪唑）衍生物被鉴定为 STAT3 信号抑制剂，其中化合物 24 对 IL-6 诱导的 JAK/STAT3 信号通路激活表现出显著的抑制作用。此外，24 抑制人肝癌细胞（HepG2）和食管癌细胞（EC109）中的癌细胞生长和迁移，并诱导细胞凋亡和细胞周期停滞。化合物 24 在不影响体重的情况下，在小鼠 HepG2 细胞异种移植肿瘤模型中也显示出明显的抗肿瘤活性。这些结果证实 24 是一种具有一定抗肿瘤活性的潜在 STAT3 信号抑制剂。
