2-Chloro-1,4-Naphthoquinone Derivative Of Quercetin As An Inhibitor Of Aldose Reductase And Anti-Inflammatory Agent
| Autor: | Lucia Kovacikova, Miroslav Veverka, Marta Soltesova Prnova, Ivana Milackova, Sreeparna Banerjee, Milan Stefek, Magdalena Majekova, Ruzena Sotnikova, Michal Stasko |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Erythrocytes Metabolite Anti-Inflammatory Agents 1 4-Naphthoquinone Kidney Tissue Culture Techniques chemistry.chemical_compound Polyol pathway Aldehyde Reductase Drug Discovery Lens Crystalline Animals Sorbitol Intestinal Mucosa Rats Wistar Pharmacology Aldose reductase Erythrocyte fragility General Medicine Colitis Rats Disease Models Animal Kinetics Osmotic Fragility Glucose chemistry Biochemistry Quercetin Naphthoquinones |
| Popis: | The ability of flavonoids to affect multiple key pathways of glucose toxicity, as well as to attenuate inflammation has been well documented. In this study, the inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxy-phenyl]-5-hydroxy-chromen-4-one (compound 1), was studied in greater detail in comparison with the parent quercetin (compound 2). The inhibition activity of 1, characterized by IC50 in low micromolar range, surpassed that of 2. Selectivity in relation to the closely related rat kidney aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated in the presence of high glucose, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner, which indicated that 1 was readily taken up by the eye lens cells and interfered with cytosolic aldose reductase. In addition, compound 1 provided macroscopic protection of colonic mucosa in experimental colitis in rats. At pharmacologically active concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy-[1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood cells. |
| Databáze: | OpenAIRE |
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