Design, Synthesis, and Biological Evaluation of Scutellarein Derivatives Based on Scutellarin Metabolic Mechanism In Vivo

被引：13

作者：

Dong, Ze-Xi ^{[1
]}

Shi, Zhi-Hao ^{[1
,2
]}

Li, Nian-Guang ^{[1
]}

Zhang, Wei ^{[1
]}

Gu, Ting ^{[1
]}

Zhang, Peng-Xuan ^{[1
]}

Wu, Wen-Yu ^{[1
]}

Tang, Yu-Ping ^{[1
]}

Fang, Fang ^{[1
]}

Xue, Xin ^{[1
]}

Li, He-Min ^{[1
]}

Cheng, Hai-Bo ^{[3
]}

Yang, Jian-Ping ^{[1
]}

Duan, Jin-Ao ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Jiangsu Key Lab High Technol Res TCM Formulae, Jiangsu Collaborat Innovat Ctr Chinese Med Resour, Natl & Local Collaborat Engn Ctr Chinese Med Reso, Nanjing 210023, Jiangsu, Peoples R China

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

[3] Nanjing Univ Chinese Med, Key Lab SATCM Empir Formulae Evaluat & Achievemen, Nanjing 210023, Jiangsu, Peoples R China

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2016年 / 87卷 / 06期

基金：

中国国家自然科学基金;

关键词：

antioxidant; scutellarein; scutellarin; solubility; thrombin; THROMBIN-INHIBITORS; NITRIC-OXIDE; SOLUBILITY; ANALOGS; ISCHEMIA/REPERFUSION; QUERCETIN; THERAPY; DISEASE; STROKE; DAMAGE;

D O I：

10.1111/cbdd.12727

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2O2-induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.

引用

页码：946 / 957

页数：12

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