摘要
为了寻找高效低毒的抗肿瘤候选化合物,我们对β-咔啉环的1,2,9三个结构位点进行了设计与合成,得到了一系列的1-取代-β-咔啉衍生物,这些化合物的结构经~1H NMR、^(13)C NMR、MS、IR及元素分析确证。采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402,HepG2,A549,A375,786-0和HT-29)活性,构效关系结果显示β-咔啉1位取代基团对抗肿瘤活性的影响趋势为:2-噻吩基>2-氯苯基>4-氯苯基>苄基。
In the present study, we designed and synthesized a series of 1-substituted-β-carboline derivatives through modification of position-l, 2 and 9 of β-carboline nucleus in order to discover novel leading compounds with better antitumor activities and less toxicity. Their structures were confirmed by 1H NMR, 13C NMR, MS, IR and elemental analyses. All the target compounds were tested for cytotoxic activity against six cancer cell lines, including Bel-7402, HepG2, A549, A375, 786-0 and HT-29 by methyl thiazolyl tetrazolium （MTT） method. Studies of structure-activity relationships indicated that the effects of substituents in position- 1 on cytotoxic activities were in an order as follows： 2-thienyl 〉2-chlorophenyl 〉4-chlorophenyl 〉benzyl group.
基金
National Science and Technology Major Projec of the Ministry of Science and Technology of China(Grant No2011ZX09401-007)
National Key Technology Research and Development Program of the Ministry of Science and Technology of China(Grant No.2012BAI30B00)
关键词
β-咔啉
合成
抗肿瘤活性
构效关系
β-Carboline, Synthesis, Anticancer activity, Structure-activity relationships
