Nitric oxide-releasing molecules

Nitric Oxide-Releasing Molecules for Cancer Therapy and Chemoprevention... 

Keywords Cancer biology Cancer chemoprevention Furoxans Nitric oxide releasing molecule (NORM) NONOate NO-NSAID Quinone methide... 

Fig. 20.8 Structures of various furoxans and nitric oxide releasing molecules (NORMs)-I...

Burgaud, J.L., Riffaud, J.P., and Soldato, P. (2002b). Nitric-oxide releasing molecules A new class of drugs with several major indications. Curr. Pharm. Des. 8, 201-213. 

Saavedra JE, Booth MN, Hrabie JA, Davies KM, Keefer LK. 1999. Piperazine as a linker for incorporating the nitric oxide-releasing diazeniumdiolate group into other biomedically relevant functional molecules. J. Org. Chem. 64 5124-31... 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

Nitric oxide (NO) is an intercellular signaling molecule that can inhibit neuronal energy production (Brorson et al., 1999 Malefic et al., 2004). It has been found that NO donors cause large increases in extracellular adenosine in cultures of forebrain neurons (Rosenberg et al., 2000). These were shown to be caused by NO release, and the accumulation of adenosine was not blocked by probenecid (ENT blocker) or GMP (a blocker of AMP hydrolysis), suggesting that adenosine was likely of intracellular origin. Indeed, it was found that NO donors caused a decrease in intracellular ATP and the inhibition of adenosine kinase activity, possibly due to the rise in adenosine. 

Intramuscular injection of turpentine causes a biphasic HPA response [33], The first phase corresponds to the stress of injection with no detectable changes in plasma IL-6 concentrations. However, the second phase coincides with an inflammatory response to the turpentine, a response accompanied by increased plasma ACTH, corticosterone, and IL-6 levels. CRH, AVP, and PGs play stimulatory roles in this model, whereas nitric oxide dampens the pituitary response [33], IL-ip may be important for triggering the release of these signaling molecules, since mice lacking the gene for IL-ip have a blunted GC response to turpentine [34],... 

N-diazeniumdiolates spontaneously dissociate at physiological pH to release nitric oxide (NO) by stable first order kinetics with half-lives ranging from 2 s to 20 h [209, 210]. They are blessed with many attributes that make them an especially attractive starting point for designing solutions to important clinical problems, namely they are stable as solids, have structural diversity, a controlled rate of release of NO on hydrolysis, and a rich derivatization chemistry that facilitates targeting of NO to specific sites of need, a critical goal for therapeutic uses of a molecule with natural bioeffector roles in virtually every organ [208]. 

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