β-咔啉杂合咪唑类化合物的合成及体外抗肿瘤活性
Synthesis and in vitro antitumor activity of β-carboline hybrid imidazole derivatives
陈亮 1郭亮 1肖艳博 1马芹 2陈伟 2张洁1
作者信息
- 1. 石河子大学 化学化工学院 新疆兵团化工绿色过程重点实验室,新疆 石河子 832003
- 2. 新疆华世丹药物研究有限责任公司,新疆 乌鲁木齐 830011
- 折叠
摘要
以L-色氨酸为原料,经Pictet-Spengler环化反应、氧化脱羧、N9-烷基化等反应步骤,合成了一系列β-咔啉杂合咪唑类化合物.目标化合物经 1HNMR、13CNMR和HRMS确证结构.采用MTT(噻唑蓝)法检测了目标化合物对肺癌细胞(A-549)、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)的体外抗肿瘤活性.结果表明,大部分化合物对这 5 种肿瘤细胞株表现出了中等及优良的抑制活性.特别是3-苄基-11-(3-苯基丙基)-11H-咪唑并[1',5':1,2]吡啶并[3,4-b]吲哚(Ⅴr)对CT-26、Bel-7402和MCF-7细胞株的体外抗肿瘤活性较高,对应的半数抑制浓度(IC50)分别为(9.5±0.4)、(7.4±0.3)和(8.8±0.6)µmol/L.分子对接结果表明,3-苄基-11-甲基-11H-咪唑并[1',5':1,2]吡啶并[3,4-b]吲哚(Ⅴa)、3-苄基-11-丁基-11H-咪唑并[1',5':1,2]吡啶并[3,4-b]吲哚(Ⅴf)和Ⅴr与VEGFR2激酶的多个氨基酸残基具有良好的结合作用.
Abstract
A series of β-carboline hybrid imidazole compounds were synthesized from L-tryptophan by Pictet-Spengler cyclization,oxidative decarboxylation and N9-alkylation,and then characterized by 1HNMR,13CNMR and HRMS.The in vitro antitumor activities of β-carboline hybrid imidazole derivatives against five cancer cell lines of lung cancer cells(A-549),stomach cancer cells(BGC-823),colon cancer cells(CT-26),liver cancer cells(Bel-7402),and breast cancer cells(MCF-7)were evaluated using thiazolylblue(MTT)method.The results showed that most of the compounds exhibited moderate to excellent activity against the tested cancer cell lines.Especially,3-benzyl-11-(3-phenylpropyl)-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴr)showed the most potent anti-proliferative activity against CT-26,Bel-7402,and MCF-7 cell lines with corresponding median inhibitory concentration(IC50)of(9.5±0.4),(7.4±0.3),and(8.8±0.6)µmol/L,respectively.Molecular docking results revealed that 3-benzyl-11-methyl-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴa),3-benzyl-11-butyl-11H-imidazo[1',5':1,2]pyrido[3,4-b]indole(Ⅴf),andⅤr had a good binding effect on several amino acid residues of VEGFR2 enzyme.
关键词
β-咔啉杂合咪唑/合成/抗肿瘤/构效关系/分子对接/医药原料Key words
β-carboline hybrid imidazoles/synthesis/antitumor/structure-activity relationship/molecular docking/drug materials引用本文复制引用
基金项目
国家自然科学基金(22067017)
兵团指导性计划(2022ZD019)
兵团第二师科技重大专项(2021SFGG01)
出版年
2024
NETL
NSTL
万方数据