Evaluation of aldose reductase inhibition and docking studies of 6'-nitro and 6',6''-dinitrorosmarinic acids.
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.
Koukoulitsa
Catherine
C
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48, Vas. Constantinou Ave, Athens 11635, Greece. koukoulitsa@eie.gr
Bailly
Fabrice
F
Pegklidou
Kiriaki
K
Demopoulos
Vassilis J
VJ
Cotelle
Philippe
P
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
D000449:Aldehyde Reductase; D002934:Cinnamates; D053630:Depsides; D004791:Enzyme Inhibitors; D000097123:Rosmarinic Acid