College of Chemistry and Environmental Science, Qujing Normal University, Qujing, People's Republic of China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, People's Republic of China.
Arch Pharm (Weinheim). 2022 Oct;355(10):e2200109. doi: 10.1002/ardp.202200109. Epub 2022 Jun 8.
A series of novel hybrid compounds between 1,4-benzodioxane and imidazolium salts was designed and prepared. The compounds were evaluated in vitro against a panel of human tumor cell lines (K562, SMMC-7721, and A-549). The structure-activity relationship results demonstrated that the 2-methyl-benzimidazole or 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-phenylphenacyl substituent were critical for promoting cytotoxic activity. Particularly, compound 25 was found to be the most potent compound with IC values of 1.06-8.31 μM against the three human tumor cell lines and exhibited higher selectivity to K562 and SMMC-7721 cells with IC values 4.5- and 4.7-fold lower than cisplatin. Moreover, compound 25 inhibited cell proliferation by inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.
设计并合成了一系列新型的 1,4-苯并二恶烷和咪唑鎓盐的混合化合物。这些化合物在体外对一组人类肿瘤细胞系（K562、SMMC-7721 和 A-549）进行了评估。结构-活性关系的结果表明，2-甲基苯并咪唑或 5,6-二甲基苯并咪唑环和咪唑基 3-位取代 4-苯基苯甲酰基取代基对于促进细胞毒性活性是至关重要的。特别是，化合物 25 被发现是对三种人类肿瘤细胞系具有最强活性的化合物，其 IC 值为 1.06-8.31 μM，对 K562 和 SMMC-7721 细胞的选择性更高，IC 值分别比顺铂低 4.5 倍和 4.7 倍。此外，化合物 25 通过诱导 SMMC-7721 细胞的 G0/G1 细胞周期停滞和凋亡来抑制细胞增殖。
