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为了寻找更好的抗肿瘤化合物,基于前期计算机辅助药物设计结果,以L-色氨酸和甲醛为原料,经过Pictet-Spengler缩合和氧化两步反应得到β-咔啉,再经过N9-烷基化反应和N2-烷基化反应得到一系列新的β-咔啉衍生物.合成的14个新的β-咔啉衍生物的结构经1H NMR,IR,MS及元素分析确证结构.利用单晶X射线衍射法测定了化合物5h的晶体结构.采用MTT法考察其对肿瘤细胞的抑制作用,实验结果表明化合物5a～5n与先导物4相比具有明显的抗肿瘤活性;用抑瘤率测定了化合物5e和5h对小鼠Lewis肺癌细胞的抑制作用,体内试验表明化合物5h具有抗Lewis肺癌作用.
In order to find a better anti-tumor compound, based on the results of computer-aided design in the early stage, β-carbolines were obtained through two steps of Pictet-Spengler condensation and oxidation with L-tryptophan and formaldehyde as raw materials, A series of new β-carboline derivatives were obtained through the chemical reaction and N2-alkylation.The structures of the 14 novel β-carboline derivatives were confirmed by 1H NMR, IR, MS and elemental analysis.Using single The crystal structure of compound 5h was determined by X-ray crystallography. The inhibitory effect of compound 5h on tumor cells was investigated by MTT assay. The results showed that compound 5a ~ 5n had obvious anti-tumor activity compared with that of leader 4; Compounds 5e and 5h inhibit Lewis lung carcinoma cells in mice, and in vivo experiments show that compound 5h has an anti-Lewis lung cancer effect.