吲哚类化合物的制备及抗肿瘤活性研究

Synthesis and antitumor activity of indole compounds

目的探索吲哚类化合物的制备及抗肿瘤活性,研发高效低毒的抗肿瘤药物。方法以不同取代基的1,3-二羰基化合物为底物,与适量2,2,6,6-四甲基哌啶氧化物(TEMPO)反应生成α-位TEMPO取代的β-二羰基化合物中间体,再与吲哚或衍生物反应,制备含不同取代基的吲哚三级醇化合物,并用甲基噻唑基四唑法检测所合成的化合物对人神经母细胞瘤细胞SHSY5Y、食管癌细胞系109、乳腺癌细胞MCF、胃癌细胞MGC的半数抑制浓度(IC50)。结果制备出8种含不同取代基的吲哚三级醇化合物,其中化合物7具有较好的细胞抑制作用。结论建立了条件温和、收率高、操作简便的吲哚类化合物合成方法,为吲哚杂环三级醇类化合物的制备及后续的药理活性研究奠定了实验基础。

Objective To investigate the preparation and antitumor activity of indole compounds,and to develop highly effective and low toxic antineoplastic agents.Methods 1,3-dicarbonyl compounds with different substituents were used as substrates to react with appropriate amount of 2,2,6,6-Tetramethylpiperidinooxy(TEMPO)to generateα-position TEMPO-substitutedβ-dicarbonyl compound intermediates,and then the indole tertiary alcohols containing different substituents were prepared by reacting with indole or derivatives.The half inhibitory concentration(IC 50)of the compound on human neuroblastoma cell line SHSY5Y,esophageal cancer cell line 109,breast cancer cell MCF and gastric cancer cell MGC was detected by methylthiazolyl tetrazole(MTT)method.Results Eight kinds of tertiary alcohol compounds with different substituents were prepared.The compound 7 has better cell inhibitory effect.Conclusion The synthesis method of indole compounds has mild conditions,high yield and simple operation;which lays the experimental foundation for the preparation of the doped heterocyclic triols and their subsequent pharmacological activity.