6-芳基-β-咔啉衍生物的合成及抗肿瘤活性研究  

Synthesis and anticancer activity of 6-Aryl-β-Carboline derivatives

作　　者：王兆旭 郭亮 孙跃 张俊婷 张洁[1] WANG Zhaoxu;GUO Liang;SUN Yue;ZHANG Junting;ZHANG Jie(School of Chemistry and Chemical Engineering/Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan,Shihezi University,Shihezi,Xinjiang 832003,China)

机构地区：[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

出　　处：《石河子大学学报（自然科学版）》2023年第6期667-677,共11页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(22067017),新疆生产建设兵团科技计划项目(2022ZD019),石河子大学高层次人才启动基金项目资助(RCZK201933)。

摘　　要：以L-色氨酸为原料,设计合成了一系列新型6-取代-β-咔啉衍生物(6a-6u)。目标化合物经^(1)H NMR,^(13)C NMR和HRMS确证结构,并采用四甲基偶氮唑盐(MTT)法测试了其体外抗肿瘤(A549、BGC-823、CT-26、Bel-7402和MCF-7)活性。结果表明,在β-咔啉环的C^(6)位引入具有吸电子取代基的苯基基团(如3,4,5-三氟苯基,6-氰基苯基)所得到的6l-6n和6t是最具潜力的化合物,其在体外抗肿瘤活性测试中分别对2株肿瘤细胞具有良好抑制作用,IC_(50)值均低于10μmol·L^(-1)。之后进行了分子对接,探究了目标化合物对VEGFR-2蛋白,PDGFR-α蛋白和KIT激酶蛋白的亲和力以及结合模式,以了解其与靶点的结合情况。A series of novelβ-carbolines possessing different substituents at R6 and N9 positions were synthesized from the L-tryptophan.All newly synthesized compounds were characterized by nuclear magnetic resonance(NMR)and High resolution mass spectra(HRMS),and antitumor activities against A549(lung carcinoma),BGC-823(gastric carcinoma),CT-26(murine colon carcinoma),Bel-7402(liver carcinoma)and MCF-7(breast carcinoma)cell lines in vitro were investigated by methyl thiazolyl tetrazolium(MTT)assay.The results demonstrated that compounds 6l-6n and 6t possessing electron-withdrawing substituents(e.g.,3,4,5-trifluorophenyl,6-cyanophenyl)at the R6-position,were found to be the most potent compounds(IC_(50) value lower than 10μmol·L^(-1) against the investigated 2 cancer cell lines).Furthermore,In order to understand the combination,molecular docking was performed to investigate their binding mode and affinities towards VEGFR-2,PDGFR-α,and KIT kinase.

关 键 词：β-咔啉 合成 抗肿瘤 构效关系 分子对接 

分 类 号：R914.5[医药卫生—药物化学]