Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-trimethyluric acid

Bhat, Vadiraja B and Sridhar, GR and Madyastha, KM (2001) Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-trimethyluric acid. In: Life Sciences, 70 (4). pp. 381-393.

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Abstract

New water-soluble analogues of 1,3,7-trimethyluric acid with N-1 methyl replaced by various groups were prepared and evaluated for their ability to scavenge hydroxyl radicals as well as their protective potential against lipid peroxidation in erythrocyte membranes. The deoxyribose degradation method indicates that all the analogues tested effectively scavenge hydroxyl radicals and some of them show better activity than uric acid and methyluric acids. These effects are shown to be concentration dependent and are more potent at low concentrations $(10-50 \hspace{2mm} \mu M)$. Among the analogues tested, 1-butenyl-, 1-propargyl- and 1-benzyl-3,7-dimethyluric acids show high hydroxyl radical scavenging property with a reaction rate constant (Ks) of $3.2-6.7 \times 10^{10} M^{-1} S^{-1}, 2.3-3.7 \times 10^{10} M^{-1} S^{-1}$ and $2.4-3.7 \times 10^{10} M^{-1} S^{-1}$, respectively. The effectiveness of these analogues as hydroxyl radical scavengers appears to be better than mannitol $(Ks, 1.9-2.5 \times 10^9 M^{-1} S^{-1})$. With the exception of 1-pentyl- and 1-(2'-oxopropyl)-3,7-dimethyluric acids, all other analogues tested are effective inhibitors of tert-butylhydroperoxide-induced lipid peroxidation in human erythrocyte membranes. All the analogues tested are susceptible to peroxidation in the presence of hemoprotein and hydrogen peroxide. The present study has pointed out that it is possible to significantly enhance the antioxidant property of 1,3,7-trimethyluric acid by structural modification at N-1 position. Such compounds may be useful as antioxidants in vivo.

Item Type: Journal Article Copyright of this article belongs to Elsevier. Hydroxyl radical;Scavenging;Lipid peroxidation;1,3,7-Trimethyluric acid analogues;Antioxidant Division of Chemical Sciences > Organic Chemistry 12 Oct 2007 19 Sep 2010 04:40 http://eprints.iisc.ernet.in/id/eprint/12197