Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors

被引：60

作者：

Shi, Zhi-Hao ^{[1
,3
]}

Li, Nian-Guang ^{[1
,2
]}

Tang, Yu-Ping ^{[1
]}

Wei-Li ^{[1
,2
]}

Lian-Yin ^{[1
]}

Yang, Jian-Ping ^{[1
]}

Hao-Tang ^{[1
]}

Duan, Jin-Ao ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Jiangsu Key Lab High Technol Res TCM Formulae, Nanjing 210046, Jiangsu, Peoples R China

[2] Nanjing Univ Chinese Med, Dept Med Chem, Nanjing 210046, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, Dept Organ Chem, Nanjing 211198, Jiangsu, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 54卷

基金：

高等学校博士学科点专项科研基金; 中国国家自然科学基金;

关键词：

Quercetin; Metabolism; Thrombin; Structure-activity relationship; STRUCTURE-BASED DESIGN; P1; POSITION; BIOAVAILABILITY; FLAVONOIDS; SCAFFOLDS; RATS; L;

D O I：

10.1016/j.ejmech.2012.04.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In blood, quercetin is mainly found in metabolized forms. In order to study the activities of these quercetin metabolites in cardiovascular disease, 17 methylquercetin derivatives were synthesized based on metabolism in vivo, their thrombin inhibition activity were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin derivatives had stronger inhibitory activities than that of quercetin. Preliminary SARs analysis showed that hydroxyl groups at C-3' and C-4' position in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles in the thrombin inhibitory activity. The findings of this study would provide information for the exploitation and utilization of quercetin as thrombin inhibitor for thrombotic disease treatment. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：210 / 222

页数：13

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