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急性髓细胞白血病是一种血液系统的恶性疾病,严重危害人类生命健康,目前尚无低毒、高效的治疗药物.靛玉红是我国传统中药青黛的有效成分,具有一定的抗白血病活性,但其水溶性差及造成的生物利用度较低,严重影响其临床应用.为了提高靛玉红的水溶性,进一步增强其抗白血病功效,在靛玉红结构中引入亲水性的胺基侧链,设计并合成了五个结构新颖的靛玉红衍生物,其结构经HRMS、~1HNMR和~(13)CNMR确证.同时,采用CCK-8法测试目标产物对急性髓系白血病HL-60细胞的体外抑制作用.结果表明,四个靛玉红衍生物具有显著的抗HL-60细胞增殖的活性,其中,化合物N1-(2-二甲氨基乙基)靛玉红(5a)的活性最强,其IC_(50)值为(3.564±0.211)μmol/L.流式细胞术和Hoechst33342染色实验显示,化合物5a能够显著诱导HL-60细胞周期阻滞和凋亡.此外,化合物5a还能影响细胞周期和凋亡相关蛋白的表达.综上研究表明,化合物5a是一个具有深入研究价值的抗白血病先导化合物.
Acute myeloid leukemia is a malignant disease of the blood system, seriously endangering the health of human life, there is no low-toxic, highly effective treatment of drugs. Indirubin is an effective component of our traditional Chinese medicine indigo, has some anti-leukemia activity, but Its poor water solubility and bioavailability caused by low, seriously affecting its clinical application.In order to improve the water solubility of indirubin and further enhance its anti-leukemia effect, the introduction of hydrophilic amine side chain in the indirubin structure, Five novel indirubin derivatives were designed and synthesized, and their structures were confirmed by HRMS, ~ 1HNMR and ~ (13) CNMR.At the same time, CCK-8 method was used to test the effect of the target product on acute myeloid leukemia HL-60 cells The results showed that the four indirubin derivatives have significant anti-proliferation activity against HL-60 cells, of which the activity of the compound N1- (2-dimethylaminoethyl) -indigoine (5a) is the strongest , And its IC 50 value was (3.564 ± 0.211) μmol / L. Flow cytometry and Hoechst33342 staining showed that compound 5a could significantly induce cell cycle arrest and apoptosis in HL-60 cells. In addition, compound 5a also affected Cell cycle and apoptosis related protein expression Studies have shown that anti-leukemia compound 5a is a lead compound has in-depth research value.