摘要/Abstract

从胡椒酸出发，通过还原、甲磺酸酯化、偶联和成盐四步反应合成了一系列新型的胡椒基咪唑盐类化合物，其结构经¹H NMR，¹³C NMR，HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选，结果表明，1-（（苯并[d][1，3]二氧杂环戊烯-5-基甲基）-3-（2-萘甲基））-5，6-二甲基-1H-苯并[d]咪唑-3-溴盐（30）具有显著的细胞毒活性，对HL-60、SMMC-7721、A-549、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂（DDP），尤其对HL-60肿瘤细胞株表现出较好的选择性细胞毒活性，其IC₅₀值约为顺铂的7.2倍.进一步研究表明，化合物30具有诱导SMMC-7721细胞株在细胞周期G0/G1期阻滞和细胞凋亡的作用.
关键词: 胡椒基, 咪唑盐, 分子杂合, 构效关系, 细胞毒活性
A series of novel hybrid compounds between piperonyl and imidazolium salts were prepared from tryptophol by four steps of reduction, mesylation, coupling and salt formation. Their structures were confirmed by ¹H NMR, ¹³C NMR, HRMS and X-ray crystallographic analysis. These compounds were evaluated in vitro against a panel of human tumor cell lines. The results showed that 1-((benzo[d] [1,3]dioxol-5-ylmethyl)-3-(2-naphthylmethyl))-5,6-dimethyl-1H-benzo[d]imidazol-3-ium bromide (30) exhibited remarkable inhibitory activity selectively against HL-60, SMMC-7721, A-549, MCF-7 and SW480 cell lines compared with DDP. In particular, the compound was more selective to HL-60 cell lines with IC₅₀ values 7.2-fold lower than DDP. Further studies showed that compound 30 has the effect of inducing SMMC-7721 cell line arrest and cell apoptosis in cell cycle G0/G1.
Key words: piperonyl, imidazolium salts, molecular hybridization, structure-activity relationship, cytotoxic activity


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