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Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids.
- Source :
-
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2013 Aug; Vol. 43 (8), pp. 661-70. Date of Electronic Publication: 2013 Jan 03. - Publication Year :
- 2013
-
Abstract
- 1. Flavonoids are a group of polyphenolic plant metabolites most commonly known for their antioxidant activities. They also show inhibitory activities on molybdo-flavoenzymes family of enzymes which are involved in biotransformation of some exogenous and endogenous chemicals. Most notably, aldehyde oxidase (AO), a member of this family, is responsible for metabolism of some therapeutic agents. On the other hand, there are some therapeutics which inhibit AO. As flavonoids are ubiquitous in human diet and have potential to interact with AO, it is important to investigate their effects at the molecular details. 2. The inhibitory effects of 15 flavonoids on the activity of rat liver AO were assessed. Quantitative structure-activity relationship studies were performed using genetic algorithm coupled partial least square and stepwise multiple linear regression methods to elucidate the important structural properties responsible for the observed inhibitory effects. To further understand the mode of interaction between these flavonoids and AO, a homology model of the enzyme was built and flavonoids were docked into its active site. The most important amino acids involved in the interactions were identified. 3. Quercetin, myricetin and genistein were the most potent inhibitors establishing favorable interactions with the enzyme. However, the glycosylated flavonoids showed relatively weaker inhibition which may be attributed to their hindered binding into the active site of AO by bulky sugar groups.
- Subjects :
- Aldehyde Oxidase chemistry
Aldehyde Oxidase metabolism
Amino Acid Sequence
Animals
Genistein chemistry
Genistein pharmacology
Humans
Inhibitory Concentration 50
Male
Molecular Docking Simulation
Molecular Sequence Data
Quercetin chemistry
Quercetin pharmacology
Rats
Rats, Sprague-Dawley
Sequence Alignment
Aldehyde Oxidase antagonists & inhibitors
Flavonoids chemistry
Flavonoids pharmacology
Quantitative Structure-Activity Relationship
Subjects
Details
- Language :
- English
- ISSN :
- 1366-5928
- Volume :
- 43
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Xenobiotica; the fate of foreign compounds in biological systems
- Publication Type :
- Academic Journal
- Accession number :
- 23282065
- Full Text :
- https://doi.org/10.3109/00498254.2012.755228