title: 2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose reductase and anti-inflammatory agent.
abstract: 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.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences , Bratislava , Slovakia .
authors.forename: Ivana
authors.initials: I
authors.lastname: Milackova
authors.forename: Marta Soltesova
authors.initials: MS
authors.lastname: Prnova
authors.forename: Magdalena
authors.initials: M
authors.lastname: Majekova
authors.forename: Ruzena
authors.initials: R
authors.lastname: Sotnikova
authors.forename: Michal
authors.initials: M
authors.lastname: Stasko
authors.forename: Lucia
authors.initials: L
authors.lastname: Kovacikova
authors.forename: Sreeparna
authors.initials: S
authors.lastname: Banerjee
authors.forename: Miroslav
authors.initials: M
authors.lastname: Veverka
authors.forename: Milan
authors.initials: M
authors.lastname: Stefek
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000187:drug effects; D005947:Glucose / Q000037:antagonists & inhibitors / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D007700:Kinetics; D007908:Lens, Crystalline / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D009996:Osmotic Fragility / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000037:antagonists & inhibitors / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D000893:Anti-Inflammatory Agents; D009285:Naphthoquinones; D013012:Sorbitol; D011794:Quercetin; D000449:Aldehyde Reductase; D005947:Glucose
keywords: Diabetic complications; flavonoids; polyol pathway