Nitrones as therapeutics.

Abstract

Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones, including alpha-phenyl-tert-butylnitrone (PBN), have been shown to have potent biological activity in many experimental animal models. Many diseases of aging, including stroke, cancer development, Parkinson disease, and Alzheimer disease, are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development for stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also, in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic-noise-induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes cannot readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our studies and others in which the use of selected nitrones as novel therapeutics has been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases.

• Authors: Robert A Floyd, Richard D Kopke, Chul-Hee Choi, Steven B Foster, Sabrina Doblas, Rheal A Towner
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 45 Issue 10 Pg. 1361-74 (Nov 15 2008) ISSN: 0891-5849 [Print] United States
• PMID: 18793715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Nitrogen Oxides
• nitrones

Topics

• Aging (drug effects)
• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Antioxidants (chemistry, pharmacology, therapeutic use)
• Hearing Loss (drug therapy)
• Humans
• Neoplasms (drug therapy)
• Nitrogen Oxides (chemistry, pharmacology, therapeutic use)
• Stroke (drug therapy)