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Inhibition of aldose reductases from rat and bovine lenses by flavonoids
- Source :
- Biochemical Pharmacology. 31:3807-3822
- Publication Year :
- 1982
- Publisher :
- Elsevier BV, 1982.
-
Abstract
- Thirty flavones, four isoflavones and thirteen coumarins were tested as inhibitors of lens aldose reductase, which is believed to participate in the initiation of cataract formation in diabetes. Many were found to be potent inhibitors, and the two most potent ones were axillarin (5,7,3′,4′-tetrahydroxy-3, 6-dimethoxyflavone) and 6,3′,4′-trihydroxy-5,7,8-trimethoxyflavone (LARI 1). These two flavones inhibited aldose reductase purified from rat lens with IC 50 values of 2.6 × 10 −8 and 3.6 × 10 −8 M respectively. They also inhibited aldose reductase purified from bovine lens with ic 50 values of 1.8 × 10 −7 M. The potencies of the two compounds were superior to those of all the previously reported inhibitors of aldose reductase. Inhibition of rat and bovine lens aldose reductases by the two compounds was of a non-competitive type with dl -glyceraldehyde as the variable substrate. Some flavones including axillarin and LARI 1 were found to be poorly or scarcely inhibitory against several adeninenucleotide-requiring enzymes, which are involved in glycolysis and other metabolic reactions. These results obtained show that the two flavones have some features which may be required in clinically useful drugs for diabetic patients. All the potent inhibitors of the compounds tested had a flavone skeleton, one (or two free) hydroxyl(s) in ring C, and more than three hydroxyls (free or methylated) in ring A. The possible relationships of structures to inhibitory potencies of the compounds tested are discussed.
- Subjects :
- Stereochemistry
Lari
In Vitro Techniques
Biochemistry
Flavones
Axillarin
Structure-Activity Relationship
chemistry.chemical_compound
Aldehyde Reductase
Coumarins
Glyceraldehyde
Lens, Crystalline
Animals
Flavonoids
Pharmacology
chemistry.chemical_classification
Aldose reductase
biology
Chemistry
Rats, Inbred Strains
Isoflavones
biology.organism_classification
Rats
Enzyme
Aldose
Sugar Alcohol Dehydrogenases
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....c5aaa7b16f91edfe32231f7bfcc6a1c9
- Full Text :
- https://doi.org/10.1016/0006-2952(82)90297-0