新型吲哚苯醌衍生物的合成及抗肿瘤活性  

Synthesis and Antitumor Activities of Novel Indole Benzoquinones Derivatives

作　　者：阮铱瞳 何菱[1] RUAN Yi-tong;HE Ling(West China School of Pharmacy,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《合成化学》2020年第5期410-415,共6页Chinese Journal of Synthetic Chemistry

基　　金：川大-泸州战略合作项目“新型小分子探针螺烯酮衍生物的合成、作用靶点以及调控肿瘤分子机制研究”(2017CDLZ-S34)。

摘　　要：基于醌类以及含"2-苯基萘型"结构单元的衍生物在临床上表现出良好的抗肿瘤活性,设计了取代吲哚苯醌衍生物。以2-取代吲哚衍生物为底物,乙腈为反应溶剂,在相转移催化剂苄基三乙基氯化铵和无水碳酸钾存在下,与四溴苯醌反应,合成了9个未见文献报道的2-取代吲哚-1,4-醌衍生物(2a^2c,3a^3c,4a^4c),其结构经1H NMR,13C NMR和HR-MS(ESI)表征。体外抗肿瘤活性实验表明,该类化合物对人肺癌细胞系(A549)、人乳腺癌细胞系(MDA-MB-231)及宫颈癌细胞系(Hela)具有抑制作用,其中化合物2b和3c对人乳腺癌细胞系MDA-MB-231具有良好的抑制活性。Quinones and derivatives containing"2-phenylnaphthalene type"structure units have good antitumor activities in the clinic.Nine novel substitued indole benzoquinones derivatives(2 a^2 c,3 a^3 c,4 a^4 c,)based on these structure units were designed and synthesized using 2-substituted indoles and tetrabromobenzoquinones as starting materials,dried acetonitrile as the solvent.The reaction was carried out under the existence of phase transfer catalyst benzyltriethylammonium chloride and alkali K2CO3 at room temperature to obtain three novel mono-indole substituted benzoquinones derivativesand six novel bis-indole substituted benzoquinones derivatives.The structures were characterized by 1H NMR,13C NMR and HR-MS(ESI).In vitro anti-tumor activity experiments showed that these compounds had inhibitory effects on human lung cancer cells A549,human breast cancer cells MDA-MB-231 and the human hela cells,among which compounds 2 b and 3 c have the best inhibitory activity on MDA-MB-231.

关 键 词：吲哚衍生物 醌类化合物 2-苯基萘型 合成 抗肿瘤活性 相转移催化 

分 类 号：O621.3[理学—有机化学] O626[理学—化学]