Chin. J. Org. Chem. ›› 2013, Vol. 33 ›› Issue (02): 332-338.DOI: 10.6023/cjoc201208035 Previous Articles     Next Articles



郭亮a, 范文玺a, 陈雪梅a, 马芹a, 曹日晖a,b   

  1. a 新疆华世丹药物研究有限责任公司 乌鲁木齐 830011;
    b 中山大学化学与化学工程学院 广州 510275
  • 收稿日期:2012-08-30 修回日期:2012-11-01 发布日期:2012-11-14
  • 通讯作者: 曹日晖
  • 基金资助:

    国家“重大新药创制”科技重大专项(No. 2009ZX09401-007)资助项目.

Synthesis and Antitumor Activities of β-Carboline Derivatives

Guo Lianga, Fan Wenxia, Chen Xuemeia, Ma Qina, Cao Rihuia,b   

  1. a Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011;
    b School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275
  • Received:2012-08-30 Revised:2012-11-01 Published:2012-11-14
  • Supported by:

    Project supported by the National Key Program for New Drug Development (No. 2009ZX09401-007).

In search of more effective antitumor agents, based on the previous results of computer aided drug design. The starting material L-tryptophan reacted with formaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the intermediate β-carboline. The intermediate was further reacted with halogenated hydrocarbon by N9-alkylation and N2-quaternarization to obtain new β-carboline derivatives. Fourteennovel β-carboline derivatives were synthesized and characterized by 1H NMR, IR, MS and elemental analysis. Compound 5h was further studied by X-ray single crystal diffraction analysis. The antitumor activity of the target compounds was studied by MTT method. The results demonstrated that N2-quaternarized compounds (5a5n) had more remarkable cytotoxic activities in vitro than 9-phenylpropyl-β-carboline (4). The tumor inhibition rates of the selected compounds 5e and 5h in mice bearing Lewis lung cancer. The compound 9 showed inhibition activity on transplanting-tumor growth of Lewis lung cancer.

Key words: β-carboline, synthesis, antitumor activity, structure-activity relationship