Novel nitric oxide synthase inhibitors: a patent review

Abstract

The NOS isoforms are attractive targets in drug design for various pathological conditions and have received considerable interest over recent years. With the advances in molecular biology, modeling software, synthesis, bioassays, and our understanding of the NOS enzymes and the function of NO, novel bioavailable and highly selective drug therapies utilizing this mode of action may soon see the light.

Fructus sophorae attenuates secretion of proinflammatory mediators and cytokines through the modulation of NF-κB and MAPK signaling pathways in LPS-stimulated RAW 264.7 macrophages

“…The presence of NO and PGE 2 is widely used as indicators of microphage activation among many inflammatory mediators (Joubert and Malan 2011;Norberg et al 2013). iNOS and COX-2 were expressed in activated macrophages, mediating the synthesis of NO and PGE 2 released into the culture medium.…”

Selective Acetamidine-Based Nitric Oxide Synthase Inhibitors: Synthesis, Docking, and Biological Studies

“…11,12 Selective inhibition of iNOS could therefore represent a feasible therapeutic strategy to treat the aforementioned and other conditions, and intense efforts to identify selective iNOS inhibitors have been carried out. 13 According to their different mechanism of action, these compounds may be divided into two major groups: molecules targeting the L-Arg binding site and acting as competitive inhibitors of the natural substrate, and inhibitors of the enzyme dimerization. 14 The first class of compounds is characterized by the presence of a guanidine-like moiety, able to mimic the L-Arg guanidine−protein interactions in the binding site.…”

An ethanol extract of <i>Aster yomena</i> (Kitam.) Honda inhibits lipopolysaccharide-induced inflammatory responses in murine RAW 264.7 macrophages

“…Stimulation of macrophages with LPS increases expression of the iNOS gene and promotes excessive NO release via decomposition of L-arginine. iNOS is also activated in response to inflammatory stimuli such as cytokines, IL, and bacterial endotoxin (33,34). In addition to its role in NO release, IL-1β also serves as one of the major pro-inflammatory cytokines released following LPS stimulation of macrophages, and its excessive production has been linked to development of chronic inflammatory diseases (35,36).…”