新型芳姜黄酮拼合吡咯螺环氧化吲哚类化合物的合成及其抗肿瘤活性
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摘要
以取代靛红和肌氨酸为原料制得1,3-偶极子,再与(E)-芳姜烯酮类化合物在乙腈中经3+2环加成反应合成了10个新型的芳姜黄酮拼合吡咯螺环氧化吲哚类化合物(3a~3j),产率70%~91%,d/r值15∶1~>20∶1,其结构经~1H NMR,~(13)C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了3a~3j对人肺癌细胞(A549)和人白血病细胞(K562)的体外抗肿瘤活性。结果表明:3f对K562抑制活性较好(IC50=31.1μmol·L-1),3b对A549抑制活性较好(IC50=54.1μmol·L~(-1))。
Ten novel turmerone motif-fused spiropyrrolidine oxindoles( 3a ~ 3j) were synthesized by 1,3-dipolar reaction of substituted isatins with sarcosine,then 3 + 2 cycloaddition with( E)-dienones in Me CN. The yields and d / r of 3a ~ 3j were 70% ~ 91% and 15 ∶ 1 ~ > 20 ∶ 1,respectively. The structures were characterized by ~1H NMR,~(13)C NMR and HR-MS( ESI-TOF). The in vitro antitumor activities against human lung cancer cells( A549) and human leukemia cells( K562) were demonstrated by MTT assays. The results showed that 3f exhibited best activity against K562 with IC50 of 31. 1 μmol·L~(-1) and 3b indicated best activity against A549 with IC50 of 54. 1 μmol·L~(-1).
Ten novel turmerone motif-fused spiropyrrolidine oxindoles( 3a ~ 3j) were synthesized by 1,3-dipolar reaction of substituted isatins with sarcosine,then 3 + 2 cycloaddition with( E)-dienones in Me CN. The yields and d / r of 3a ~ 3j were 70% ~ 91% and 15 ∶ 1 ~ > 20 ∶ 1,respectively. The structures were characterized by ~1H NMR,~(13)C NMR and HR-MS( ESI-TOF). The in vitro antitumor activities against human lung cancer cells( A549) and human leukemia cells( K562) were demonstrated by MTT assays. The results showed that 3f exhibited best activity against K562 with IC50 of 31. 1 μmol·L~(-1) and 3b indicated best activity against A549 with IC50 of 54. 1 μmol·L~(-1).
引文
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[12]刘雄伟,周根,姚震,等.异噁唑拼接吡咯螺环氧化吲哚化合物的合成及起抗肿瘤活性[J].合成化学,2016,24(5):22-31.
[13]Mosman T J.Rapid colorimetric assay for eellulair growth and survival:Application and cytotxicity assays[J].Immunol Methods,1983,65:55-63.
[14]Alley M C,Scudiero D A,Monks A,et al.Feasibility of drug screening with panals of human tumor cell lines using a mycroculture tetrazolium assay[J].Cancer Res,1988,48:589-601.