黄芩苷衍生物的合成及其生物活性研究

Synthesis and evaluation of biological activity of baicalin derivatives

目的为改善黄芩苷的溶解性，设计合成系列黄芩苷衍生物，并评价其抗脂质过氧化活性和抗肿瘤活性。方法以黄芩苷和环氧乙（丙）烷为原料，通过羟乙基化、羟丙基化、酯化反应合成了一系列黄芩苷衍生物；分别采用生化法和台盼蓝染色法测试目标化合物对小鼠脑脂质过氧化产物丙二醛（MDA）的体外抑制作用及对白血病细胞HL-60的生长抑制活性。结果合成了13个黄芩苷衍生物，其结构经H-NMR和MS确证。其中，化合物3～6、11-13为未见文献报道的新化合物。化合物1、6对MDA的抑制作用显著，化合物7-10、12具有中等强度的抑制HL-60生长作用。结论黄芩苷结构中的酚羟基是其抑制脂质过氧化产物MDA的活性基团，葡萄糖醛酸的6位游离羧基是能够增强化合物抗肿瘤活性的有效基团。

Baicalin showed many pharmacological activities, such as anti-inflammatory, eliminating oxygen free radicals ,relieving the organization＇s ischemia-reperfusion injury, adjusting immunity ,anti-tumor and an- ti-HIV activities, etc. In order to improve its solubility and bioavailability, thirteen baicalin derivatives were designed and synthesized by hydroxyethylation,hydroxypropylation or esterification. Among them,3 -6 and 11 - 13 are new compounds. Most of them were evaluated for inhibition of lipid peroxidation products MDA in mouse＇s brain and growth inhibitory activity against leukemia HL-60 cells line. Compounds 1 （R1 = OCH2 CH2 OH, R2 = OH, R3 = GluA） and 6 [ Rt = OCH2 CH （ CH3 ） OH, R2 = OH, R3 = GIuA ~ showed sig- nificant inhibition on MDA, while compounds 7 - 10 I R4 = R5 = OH, R6 = CH3, CH2CH3, CH （ CH3 ）2, （ CH2 ） 3CH3 ] and 12 （ R4 = R5 = OCH2CH2OH ,R6 = CHzCH3 ） showed moderate growth inhibitory activity against HL-60 cells. The phenolhydroxy was an essential group for the inhibition of lipid peroxidation.