Synthesis and evaluation of benzoxazinone derivatives on activity of human neutrophil elastase and on hemorrhagic shock-induced lung injury in rats

被引：29

作者：

Hsieh, Pei-Wen ^{[1
]}

Yu, Huang-Ping ^{[2
,3
]}

Chang, Yi-Ju ^{[1
]}

Hwang, Tsong-Long ^{[1
]}

机构：

[1] Chang Gung Univ, Grad Inst Nat Prod, Tao Yuan 333, Taiwan

[2] Chang Gung Mem Hosp, Dept Anesthesiol, Tao Yuan 333, Taiwan

[3] Chang Gung Univ, Coll Med, Tao Yuan 333, Taiwan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 07期

关键词：

Human neutrophil elastase; Benzoxazinones; Superoxide anion; Hemorrhagic shock; Anti-inflammatory agents; ALTERNATE SUBSTRATE-INHIBITORS; IN-VIVO; SERINE PROTEASES; DESIGN;

D O I：

10.1016/j.ejmech.2010.03.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of benzoxazinone analogs were designed, synthesized, and assayed to determine their effects on superoxide anion generation and neutrophil elastase (NE) release in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-activated human neutrophils. Of these, compounds 6-10 showed a potent dual inhibitory effect on NE release and superoxide anion generation. In contrast, compounds 11-15 exhibited highly selective and potent inhibitory activities on NE release. These results indicate that the inhibitory activity on NE release in FMLP-activated human neutrophils depended on the position of chloro-substituent in the A ring. On the other hand, 13 significantly attenuated the increase in myeloperoxidase (MPO) activity and edema in the lung of rats after trauma-hemorrhagic shock. Therefore, these compounds could be developed as new NE inhibitors. (c) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：3111 / 3115

页数：5

共 32 条

[1] Synthesis and in vitro and in vivo evaluation of the 2-(6′methoxy-3′,4′dihydro-1′-naphtyl)-4H-3,1-benzoxazin-4-one as a new potent substrate inhibitor of human leukocyte elastase [J].