黄芩素含氮衍生物的合成

目的为开发黄芩素为母体的抗肿瘤药物奠定基础。方法首先制备卤代的含氮中间体R1R2N(CH2)nCl.HCl,使之与黄芩素的6位或7位酚羟基反应,引入氮原子到黄芩素的A环。并用四甲基偶氮唑盐微量酶反应比色法3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT]测定合成产物体外抑制人肝癌细胞HepG2和人肺腺癌细胞A549细胞的活性。结果合成了10个黄芩素含氮衍生物(4a-4f,5a-5d),并经波谱测试确证其结构,均为新化合物。初步活性测试显示4c,5d有较显著的细胞毒性提升。结论该方法提供了一类新的黄芩素衍生物,能够用来制备黄芩素衍生物有机酸盐,改善母体溶解度不佳的缺点,并在药理活性方面有开发潜力。

Synthesis of nitrogen-containing baicalein analogues

Objective To study the anti-tumor baicalein analogues. Methods Baicalein derivatives were synthesized from baicalein via alkylation with nitrogen-containing side chain (R₁R₂N(CH₂)nCl·HCl). Cancer cell lines including HepG2 and A549 were incubated with baicalein analogues of various concentrations. The inhibition rate was examined by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) assay. Results Ten new baicalein analogues (4a-4f , 5a-5d) were prepared and their structures were confirmed by ¹H-NMR and ESI-MS. Activity tests showed that 4c and 5b had more significant upgraded cytotoxicity. Conclusions Series of novel baicalein derivatives can be obtained by this synthetic route. The route can be used for the synthesis of water-soluble analogue of baicalein through the reaction with mineral acid or organic acid.