5-氯-β-咔啉衍生物的合成、晶体结构与抗肿瘤活性
收稿日期: 2020-06-15
修回日期: 2020-08-06
网络出版日期: 2020-08-27
基金资助
石河子大学科研计划(SHYL-YB201804); 教育部长江学者和创新团队发展计划(IRT15R46); 石河子大学长江学者研究(CJXZ201601)
Synthesis, Crystal Structure and Antitumor Activity of Novel 5-Chloro-β-carboline Derivatives
Received date: 2020-06-15
Revised date: 2020-08-06
Online published: 2020-08-27
Supported by
the Scientific Research Innovation Project in Shihezi University(SHYL-YB201804); the Program for Changjiang Scholars and Innovative Research Team in University(IRT15R46); the Yangtze River Scholar Research Project of Shihezi University(CJXZ201601)
以1-甲基- β-咔啉为原料, 经过硝化、 N 9-烷基化反应和还原胺化反应等步骤, 合成了一系列新型的5-氯- β-咔啉衍生物, 目标化合物的结构经 1H NMR, 13C NMR以及HRMS确证, 并利用单晶X射线衍射分析了 N-(吡啶-3-基)甲基-5-氯-1,9-二甲基- β-咔啉-6-胺(5e)的精确结构. 采用噻唑蓝(MTT)法测试了目标化合物对肺癌细胞A549、胃癌细胞BGC-823、结肠癌细胞CT-26、肝癌细胞Bel-7402和乳腺癌细胞MCF-7的细胞增殖抑制作用. 实验结果表明, 部分化合物具有较好的抗肿瘤活性, 其中 N-(2,6-二氟苄基)-1-甲基-5-氯-9-(2,3,4,5,6-五氟苄基)- β-咔啉-6-胺(5j)和 N-(吡啶-3-基甲基)-1-甲基-5-氯-9-(2,3,4,5,6-五氟苄基)- β-咔啉-6-胺(5m)对所测试的4种肿瘤细胞株均有较高的抑制活性, IC50值均小于10 µmol•L –1.
孙跃 , 郭亮 , 范文玺 , 陈伟 , 张洁 , 代斌 . 5-氯-β-咔啉衍生物的合成、晶体结构与抗肿瘤活性[J]. 有机化学, 2021 , 41(1) : 400 -406 . DOI: 10.6023/cjoc202006026
Sixteen novel 5-chloro- β-carboline derivatives were synthesized from harmane in four steps: N 9-alkylation, nitration, reduction, and Borch reduction. The structures of target compounds were confirmed by 1H NMR, 13C NMR, and HRMS. A single crystal of 5-chloro-1,9-dimethyl- N-(pyridin-3-ylmethyl)- β-carboline (5e) was cultured, and its single crystal structure was determined by X-ray diffraction study. The in vitro antiproliferative activities were evaluated in a panel of cancer cell lines (A549, BGC-823, CT-26, Bel-7402, and MCF-7) via methyl thiazolyl tetrazolium (MTT) assay. The results indicated that some compounds had good activities, and especially N-(2,6-difluorobenzyl)-1-methyl-5-chloro-9-(2,3,4,5,6-pentafluorobenzyl)- β- carboline-6-amine (5j) and N-(pyridin-3-ylmethyl)-1-methyl-5-chloro-9-(2,3,4,5,6-pentafluorobenzyl)- β-carboline-6-amine (5m) showed considerable antitumor activity with IC50 values lower than 10 μmol•L –1 against four cancer cell lines.
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