Cemtirestat, a novel aldose reductase inhibitor and antioxidant, in multitarget pharmacology of diabetic complications

jm-2014-015814_0007Fifteen compounds, sharing an indole-1-acetic acid moiety as a common fragment, were selected from commercial databases for testing aldose reductase inhibition. 3-Mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid was the most promising inhibitor, with an IC50 in the submicromolar range and high selectivity, relative to aldehyde reductase. The crystal structure of aldose reductase complexed with cemtirestat revealed an interaction pattern explaining its high affinity. Physicochemical parameters underline the excellent “leadlikeness” of cemtirestat as a promising candidate for further structure optimizations.
DOI: 10.1021/jm5015814

Influence of tiopronin, captopril and levamisole therapeutics on the oxidative degradation of hyaluronan

The results of ABTS and DPPH assays show the highest radical scavenging activity for captopril, followed by tiopronin. For levamisole, no effect was observed. Captopril and tiopronin prevented hyaluronan degradation induced by •OH radicals in a similar manner, while tiopronin was more effective in scavenging peroxy-type radicals.
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A new mechanism involved in the anti-inflammatory activity of hydroxychloroquine

neutrofilHydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis.
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Therapeutic potential of 3′-O-(3-chloropivaloyl)quercetin as a novel antiinflammatory drug in neurodegenerative diseases

BV-2Chronic inflammation in brain plays a critical role in major neurodegenerative diseases such as Alzheimer’s, Parkinson’s disease, stroke or multiple sclerosis. Microglia, resident macrophages and intristinc components of CNS, appear to be main effectors in this pathological process. Quercetin, a naturally occurring flavonoid, was proven to downregulate inflammatory genes in microglia. Synthetically modified quercetin, 3′-O-(3-chloropivaloyl) quercetin (CPQ), is assumed to possess better biological availability and enhanced antioxidant properties.
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