Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2014 Vol: 6 Issue: 5

In vitro and in vivo evaluation of antioxidant activity of ARIs: Benzothiadiazine and pyridothiadiazine derivatives

Abstract

Increased oxidant stress plays an important role in the chronic complications of diabetes. This study aimed to examine if our previously synthesized aldose reductase inhibitors( ARIs), benzothiadiazine 1,1-dioxide derivatives and the structural analogues pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide derivatives, have the potent as antioxidants. Several assays have been used to estimate antioxidant capacities including DPPH, MDA and Sorbitol assays. Effect of concentration, PH and sunlight on DPPH scavenging activity were determined, and results showed Benzothiadiazine 1,1-dioxide derivatives(compound 7a, 7b, 7c) at both concentration of 10-5M and10-4M had notable scavenging activity against DPPH, significantly higher than that of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide derivatives(compound 7’a,7’b,7’c). The PH demonstrated no effect on the activity and sunlight was essential for the activity. The brain MDA levels (MDA, an index of lipid peroxidation) for compounds 7a, 7b, 7c significantly decreased comparing with the negative control, the brain homogenate sample induced by oxidant system Fe(Ⅲ) ascorbic acid. Oral administration of compound7’a,7’b and7’c to groups of STZ-induced rats for 5 days decreased the level of sciatic nerve sorbitol, The inhibition of sorbitol level in the range of 24%-35% for7’a,7’b and7’c, showing some difference with the in vitro study.