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.
Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Cinnamates/pharmacology , Depsides/pharmacology , Enzyme Inhibitors/pharmacology , Binding Sites , Cinnamates/chemistry , Depsides/chemistry , Drug Evaluation, Preclinical , Enzyme Inhibitors/chemistry , Models, Molecular , Rosmarinic AcidABSTRACT
The potential role of 2-methyl imidazole in improving lycopene production by Blakeslea trispora with regards to yield, selectivity, and safety aspects was investigated in batch culture. Optimization of the bioprocess conditions in terms of (a) (+) and (-) strain ratio in the inoculum, (b) initial crude soybean oil (CSO) addition level, and (c) the amount of 2-methyl imidazole was based on response surface methodology to achieve maximum lycopene production. The dependence of growth kinetics, lycopene yield, and selectivity of the bioprocess on the above factors was clear. 2-Methyl imidazole at 50 mg/L was found equally active in terms of lycopene cyclase inhibition with that at 200 or 100 mg/L; in all cases, lycopene accounted for 94% of the total carotenoids. The highest yield was observed at a 50 mg/L level of addition (24 mg/g of biomass dry weight,) in a substrate supplemented with CSO (48 g/L of culture medium) and inoculated with 1(+)/7(-) strain ratio.
