Nitric Oxide‐Releasing Drugs

Abstract

Nitric oxide (NO) deficiency has been implicated in many pathologic processes, thus providing a solid biological basis for the use of NO replacement therapy. Exogenous NO sources constitute a powerful way to supplement NO when the body cannot generate sufficient NO for normal biological functions. This theory has opened up the possibility of designing new drugs that are capable of delivering NO into tissues and the bloodstream in a sustained and controlled manner. This objective has been achieved by grafting an organic nitrate structure onto existing drugs through chemical spacers, such as aliphatic, aromatic, or a heterocyclic chain. The approach has led to the synthesis of several new chemical entities whose pharmacologic profile challenges the parent drug, not only on the basis of new properties, but also with respect to a better safety profile. In this article, a specific class of NO donors is reviewed, the nitric oxide-releasing non-steroidal antiinflammatory drugs, NO-NSAIDs. Recently discovered compounds, whose action depends on the combined properties of both the known drug and NO release, are illustrated. Two examples are described in detail: (1) nitric oxide-releasing aspirin, which has demonstrable innovative properties for treatment of vascular disorders and cancer; (2) nitro-derivatives of flurbiprofen that have shown encouraging results in models of Alzheimer's disease.

Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals

“…Therefore, the possibility of generating new, metabolically active mitochondria might improve the outcome of these pathologies. In this context, it is interesting that BAY 41-2272 and new NO donor compounds have potential clinical application (50,51).…”

Characterization of folate-graft-chitosan as a scaffold for nitric oxide release

“…Metal complexes, nitrosothiols, nitrosamines, and diazeniumdiolates were all examples of molecular structures that had been developed as effective NO donors [8]. Such "NO donors" facilitated the improved understanding of NO's function in biological systems and might potentially serve as therapeutic agents for a number of disease states [9,10]. Diazeniumdiolate NO donors were particularly attractive because they dissociated spontaneously under physiological conditions (i.e., 37 • C, pH 7.4) to yield two moles of NO per mole of NO donor [11].…”

Functional models of [Fe—S] nitrosyl proteins

“…32, 33 Investigations into the structures and physicochemi cal properties of synthetic models of active sites of non heme [Fe-S] nitrosyl proteins are related to application of knowledge in practice for the selective delivery of nitro gen monoxide in vivo. [34][35][36][37][38][39][40][41][42][43][44][45] In recent years, a search for, and studies of, new nitrogen monoxide donors have at tracted considerable attention of experts in practical medi cine. There are several classes of compounds that gener ate nitrogen monoxide during metabolic processes.…”