关键词：
β-咔啉;合成;抗肿瘤;构效关系;分子对接
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 C6 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,IC50 值均低于 10 μmol·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.
译 名：
Synthesis and anticancer activity of 6-Aryl-β-Carboline derivatives
关键词：
β-carboline%synthesis%antitumor%structure-activity relationship%molecular docking
摘 要：
A series of novel β-carbolines possessing different substituents at R6 and N9 positions were synthesized from the L-trypto-phan.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 carcino-ma),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-trif-luorophenyl,6-cyanophenyl)at the R6-position,were found to be the most potent compounds(IC50 value lower than 10 μmol·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.
