去氢骆驼蓬碱衍生物的合成和抗肿瘤活性研究

Synthesis and Antitumor Activities of Harmine Derivatives

目的合成去氢骆驼蓬碱衍生物并研究其抗肿瘤活性。方法以去氢骆驼蓬碱为原料,在NaH催化下先用卤代烷烃对9位氮原子进行烷基化,然后用溴化苄将2位氮原子进行季铵化,得到一系列去氢骆驼蓬碱衍生物,用MTT法考察其对肿瘤细胞的抑制作用。结果合成了6个新的去氢骆驼蓬碱衍生物,结构经1H-NMR、MS和红外光谱确证。与去氢骆驼蓬碱相比,所合成的化合物均有明显的抗肿瘤活性。结论初步药理实验结果表明去氢骆驼蓬碱9-苯丙基取代能够明显提高抗肿瘤效果。

OBJECTIVE To synthesize a series of harmine derivatives and determine their antitumor activity. METHODS The target compounds were synthesized from the starting material harmine by reaction with halogenated hydrocarbon in the presence of sodium hydride in DMF, and then quaternarized with benzyl bromide in ethyl acetate. The antitumor activity of the target compounds was studied by MTT method. RESULTS Six novel harmine derivatives were synthesized, and their structures were characterized by 1H-NMR, MS and IR spectra. All compounds had more potent cytotoxic activities in vitro than harmine. CONCLUSION The preliminary results showed that the phenylpropyl substituent at position-9 increased antitumor activity.