Anti-Inflammatory Activity of a New Class of Nitric Oxide Synthase Inhibitors That Release Nitric Oxide

被引：12

作者：

Botta, Maurizio ^{[1
]}

Distrutti, Eleonora ^{[3
]}

Mencarelli, Andrea ^{[2
]}

Parlato, Maria Cristina ^{[1
]}

Raffi, Francesco ^{[1
]}

Cipriani, Sabrina ^{[2
]}

Fiorucci, Stefano ^{[2
]}

机构：

[1] Univ Siena, Dipartimento Farmacochimicotecnol, I-53100 Siena, Italy

[2] Univ Perugia, Dipartimento Med Clin & Sperimentale, I-06121 Perugia, Italy

[3] Osped Santa Maria Misericordia, Azienda Osped Perugia, I-06121 Perugia, Italy

来源：

CHEMMEDCHEM | 2008年 / 3卷 / 10期

关键词：

apoptosis; inflammation; nitric oxide; NOS inhibitors;

D O I：

10.1002/cmdc.200800201

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Nitric oxide (NO) is a gaseous mediator that exerts key regulatory functions in mammalian cells. Low levels of NO exert homeostatic functions and counteract inflammation, whereas high amounts of NO cause tissue destruction and cellular death. Herein we describe a new class of nitric oxide synthase (NOS) inhibitor NO-donoting drugs (NI-NODs). Human endothelial cells and human monocyte-based activity screening showed that NI-NODs inhibit IL-1 beta production, modulate PGE(2) production, and protect against apoptosis. In a rodent model of colitis, NI-NOD1 and NI-NOD2 potently decreased inflammation. These data show that NI-NODs are effective in both in vitro and in vivo models of inflammation, mimicking the positive effects of low levels of NO and suppressing NOS-induced NO production.

引用

页码：1580 / 1588

页数：9

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