title: Evaluation of aldose reductase inhibition and docking studies of 6'-nitro and 6',6''-dinitrorosmarinic acids.
abstract: Aldose reductase (ALR2) of the polyol metabolic pathway is a target enzyme for the treatment of diabetic complications. A variety of synthetic and natural compounds have been observed to inhibit aldose reductase. Among them, rosmarinic acid has been shown to be in vitro an aldose reductase inhibitor in a micromolar range. In this study, two nitro derivatives of rosmarinic acid synthesized previously, 6'-nitro and 6',6''-dinitrorosmarinic acids, are proposed as aldose reductase inhibitors. Docking studies of the nitro derivatives have been carried out in the active site of aldose reductase. The theoretical results have shown a higher estimated binding energy of both compounds in comparison to that of rosmarinic acid suggesting a higher ALR2 inhibitory activity. The in vitro biological assays confirmed that these compounds were more potent than the parent rosmarinic acid.
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48, Vas. Constantinou Ave, Athens 11635, Greece. koukoulitsa@eie.gr
authors.forename: Catherine
authors.initials: C
authors.lastname: Koukoulitsa
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bailly
authors.forename: Kiriaki
authors.initials: K
authors.lastname: Pegklidou
authors.forename: Vassilis J
authors.initials: VJ
authors.lastname: Demopoulos
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D000097123:Rosmarinic Acid
chemical_list: D000449:Aldehyde Reductase; D002934:Cinnamates; D053630:Depsides; D004791:Enzyme Inhibitors; D000097123:Rosmarinic Acid