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Anti‐Inflammatory Activity of a New Class of Nitric Oxide Synthase Inhibitors That Release Nitric Oxide
Author(s) -
Botta Maurizio,
Distrutti Eleonora,
Mencarelli Andrea,
Parlato Maria Cristina,
Raffi Francesco,
Cipriani Sabrina,
Fiorucci Stefano
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800201
Subject(s) - nitric oxide , nitric oxide synthase , inflammation , mediator , in vivo , nod , chemistry , in vitro , monocyte , apoptosis , pharmacology , microbiology and biotechnology , biochemistry , biology , immunology , organic chemistry , gene
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‐donating drugs (NI‐NODs). Human endothelial cells and human monocyte‐based activity screening showed that NI‐NODs inhibit IL‐1β production, modulate PGE 2 production, and protect against apoptosis. In a rodent model of colitis, NI‐NOD 1 and NI‐NOD 2 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.