摘要
以L-色氨酸和4-氯苯甲醛为原料,经过Pictet-Spengler缩合和氧化脱羧两步反应得到1-(4-氯苯基)-β-咔啉,再经过N9-烷基化和N2-烷基化反应得到12个新的1-(4-氯苯基)-β-咔啉衍生物。目标化合物的结构经1H NMR、元素分析和MS鉴定。采用MTT法考察其对肿瘤细胞的抑制作用,实验结果表明β-咔啉环的N2-烷基化能明显提高抗肿瘤效果,是该类化合物的主要活性位点。
The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-（4-chlorophenyl）-β-carboline.The intermediate was further reacted with alkyl halogenide by N9-alkylation and N2-quaternarization to obtain 12 novel 1-（4-chlorophenyl）-β-carboline derivatives.The chemical structures of all target compounds were characterized by elemental analyses,MS and 1H NMR spectra.The antitumor activities of the target compounds were evaluated by MTT method.The results demonstrated that N2-quaternarized compounds enhanced the antitumor activity significantly.In particular,compound 15 was found to be the most potent compound with IC50 values lower than 5 μmol.L 1 against 6 human tumor cells.These results confirmed that the N2-alkyl or aralkyl substituent on the β-carboline ring played an important role in the modulation of the antitumor activities.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第1期77-82,共6页
Acta Pharmaceutica Sinica
基金
国家"重大新药创制"科技重大专项(2011ZX09401-007)
兵团科技攻关项目(2011BA042)
关键词
β-咔啉
抗肿瘤活性
构效关系
β-carboline
antitumor activity
structure-activity relationship
