含吲哚三级醇的合成和抗肿瘤活性评价  

Synthesis and anti-tumor activity evaluation of indole-containing tertiary alcohols

作　　者：庄方方[1] 尹延彦[1] 闫建伟[1] 闫福林[1] 

机构地区：[1]新乡医学院药学院,河南新乡453003

出　　处：《新乡医学院学报》2016年第4期267-271,共5页Journal of Xinxiang Medical University

基　　金：国家自然科学基金资助项目(编号:81172953)

摘　　要：目的合成一系列含吲哚环的三级醇,进行抗肿瘤活性测试,考察其结构与活性的关系。方法 (1)制备目标产物:吲哚,1,3-二羰基化合物和2,2,6,6-四甲基哌啶-1-氧自由基(TEMPO)一锅法合成吲哚3-位取代的三级醇;(2)抗癌活性筛选:用四唑盐比色法对制备的3-位取代的吲哚衍生物进行多种癌瘤细胞株的体外细胞毒活性试验。结果共合成14个化合物,通过对人类神经母细胞瘤细胞(SHSY5Y)、食管癌细胞系(109)、乳腺癌细胞(MCF)和胃癌肿瘤细胞(MGC)4种细胞系的测定,发现部分化合物具有不同程度的抗肿瘤活性。其中吲哚衍生物5、6、7对SHSY5Y、109、MCF、MGC 4种肿瘤细胞抑制效果逐渐增强;吲哚衍生物中化合物15对109细胞的IC50达到8.42μmol·L-1。结论丙酰乙酸乙酯衍生7、6-氯及6-溴吲哚衍生物14和15有较好的抗肿瘤活性。Objective A series of indole-containing tertiary alcohols were synthesized and their antitumor activities were tested to investigate their structure-activity relationship. Methods（ 1） The preparation of targeted products： indole 3-substituted tertiary alcohols were synthesized through one-pot procedure from indoles,1,3-dicarbonyl compounds and 2,2,6,6-tetramethyl-1-piperidyloxy（ TEMpo）.（ 2） Screening of antitumor activity： cytotoxic activities of the preparation 3-subtituted indole derivatives were tested in four different cancer cell lines in vitro by 3-（ 4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide method. Results Fourteen desired compounds were prepared and their antitumor activities were evaluated against human neuroblastoma（ SHSY5Y）,esophageal carcinomacell line（ 109）,gastric cancer cell（ MGC） and breast carcinoma cell（ MCF） in vitro. Several compounds showed different antitumor activities. Indole derivatives 5,6 and 7 against the four kinds of tumor cells inhibition effect were increased gradually,howerer,the IC50 of 15 against 109 decreased to 8. 42 μmol·L- 1in compound 11- 16. Conclusion Ethyl propionylacetate derivative（ compound 7） and 6-Cl and 6-Br indole derivatives（ compound 14,15） exhibit good antitumor activities.

关 键 词：吲哚 1 3-二羰基化合物 合成 含吲哚三级醇 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]