黄芩苷衍生物的合成及其抗人类免疫缺陷病毒（HIV-1）活性评估

[Synthesis of baicalin derivatives and evaluation of their anti-human immunodeficiency virus (HIV-1) activity].

作者信息

Zhao J, Zhang Z, Chen H, Zhang X, Chen X

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050.

出版信息

Yao Xue Xue Bao. 1998;33(1):22-7.

PMID:11938930

Abstract

The aglycone baicalien(1) and the key intermediate 5,6-O-dibenzyl-baicalien(3) were prepared from baicalin in order to evaluate the influence of different glycosyloxies linked to baicalien on anti-HIV activity. Four new flavone-glycosides namely 5-hydroxyl-6-O-benzyl-flavone-7-beta-D-glucoside(12), 5-hydroxyl-6-O-benzyl-flavone-7-beta-D-galactoside(13), 5-hydroxyl-6-O-benzyl-flavone-7-alpha-D-mannoside(14) and 5-hydroxyl-6-O-benzyl-flavone-7-alpha-D-arabinoside (15) were synthesized by condensation of the corresponding protected glycosyl bromides with (3). Biological activity test showed that (a) both baicalin and baicalien inhibited HIV-1 RT; (b) the 6-hydroxyl substitution of baicalin and baicalien is necessary for their inhibitory activity on HIV-1 RT; (c) the HIV-1 inhibitory activity and cytotoxicity of baicalien were higher than those of baicalin, the two compounds were found to have almost identical therapeutic index.

摘要

为了评估与黄芩苷元相连的不同糖氧基对抗HIV活性的影响，从黄芩苷制备了苷元黄芩苷元（1）和关键中间体5,6 - O - 二苄基 - 黄芩苷元（3）。通过相应的保护糖基溴化物与（3）缩合，合成了四种新的黄酮苷，即5 - 羟基 - 6 - O - 苄基黄酮 - 7 - β - D - 葡萄糖苷（12）、5 - 羟基 - 6 - O - 苄基黄酮 - 7 - β - D - 半乳糖苷（13）、5 - 羟基 - 6 - O - 苄基黄酮 - 7 - α - D - 甘露糖苷（14）和5 - 羟基 - 6 - O - 苄基黄酮 - 7 - α - D - 阿拉伯糖苷（15）。生物活性测试表明：（a）黄芩苷和黄芩苷元均抑制HIV - 1逆转录酶；（b）黄芩苷和黄芩苷元的6 - 羟基取代对于它们对HIV - 1逆转录酶的抑制活性是必需的；（c）黄芩苷元的HIV - 1抑制活性和细胞毒性高于黄芩苷，发现这两种化合物具有几乎相同的治疗指数。