Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, PR China; Key Laboratory for Forest Resources Conservation and Utilisation in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming, China.
Eur J Med Chem. 2019 Apr 15;168:232-252. doi: 10.1016/j.ejmech.2019.02.025. Epub 2019 Feb 11.
Sixty-one novel steroidal imidazolium salt derivatives were synthesized and evaluated in vitro against a panel of human tumor cell lines. The results showed that diosgenin‒imidazolium salt derivatives displayed much higher cytotoxic activities than cholesterol‒imidazolium salts and dehydroepiandrosterone‒imidazolium salts. The SARs results suggested that the existence of substituted 5,6-dimethyl-benzimidazoles or benzimidazole ring and substitution of the imidazolyl-3α-position with a 2-bromobenzyl or 2-naphthylmethyl group could be critical for promoting cytotoxic activity. Diosgenin‒imidazolium salt a30 was found to be the most potent compound with IC values of 0.44-0.79 μM against five human tumor cell lines. Compound a24 showed inhibitory activity selectively against SMMC-7721 cell lines with IC value of 0.21 μM and 54-fold more sensitive to DDP. Moreover, compound a30 inhibited cell proliferation through inducing the G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.
合成了 61 种新型甾体咪唑盐衍生物，并在体外对一系列人肿瘤细胞系进行了评估。结果表明，薯蓣皂苷元-咪唑盐衍生物的细胞毒性活性明显高于胆固醇-咪唑盐和去氢表雄酮-咪唑盐。构效关系研究结果表明，取代的 5,6-二甲基苯并咪唑或苯并咪唑环的存在以及咪唑基 3α-位取代 2-溴苄基或 2-萘甲基基团对于促进细胞毒性活性可能是至关重要的。薯蓣皂苷元-咪唑盐 a30 被发现是对五种人肿瘤细胞系具有最强活性的化合物，IC 值为 0.44-0.79 μM。化合物 a24 对 SMMC-7721 细胞系具有选择性抑制活性，IC 值为 0.21 μM，对 DDP 的敏感性增加了 54 倍。此外，化合物 a30 通过诱导 SMMC-7721 细胞的 G0/G1 细胞周期阻滞和凋亡来抑制细胞增殖。
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