姜黄酮骨架双螺环吡咯氧化吲哚类化合物的合成及其抗白血病活性研究

Synthesis and Anti-human Leukemia Cells Activities of Turmerone Motif-fused 3,3'-Pyrrolidinyl-dispirooxindoles

本文以各种取代的靛红1、二烯酮3-烯基氧化吲哚2与脯氨酸或硫代脯氨酸,在有机溶剂乙腈中回流,进行1,3-偶极子3+2环加成反应,获得6个新型的姜黄酮骨架双螺环吡咯氧化吲哚类化合物(3a^3f,Scheme 1),产率65~81%,dr值10∶1~15∶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^3f对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:化合物3a对K562具有一定的抑制活性(IC50为27.9μM),接近于阳性对照药顺铂。

Six novel turmerone motif-fused 3,3＇-pyrrolidinyl-dispirooxindoles（ 3 a - 3 f） were synthesized via a multicomponent 1,3-dipolar cycloaddition event of dienones 2 with azomethine ylides（ thermally generated in situ from isatins 1 and proline or thioproline）. The yields and dr of 3 a - 3 f were 65% - 81% and 10 ∶1 - 15∶1,respectively. The structures were characterized by 1 H NMR,13 C NMR and HR-MS（ ESI-TOF）. The in vitro antitumor activities against human leukemia cells（ K562） were demonstrated by MTT assays. The results showed that 3 a exhibited well inhibition activities against K562,showing IC50 27. 9 μM,and showed equipotent potent than the positive control of Cisplatin.