In Vitro and In Silico Studies to Explore Structural Features of Flavonoids for Aldehyde Oxidase Inhibition

Abstract

Aldehyde oxidase (AO), an important enzyme in the biotransformation of drugs and xenobiotics, is inhibited by flavonoids. This enzyme can metabolize both aldehydes and N-heterocycles. In this work, a set of 15 flavonoids was assessed for inhibitory activity on the AO oxidation of vanillin as an aldehyde substrate. Spectrophotometrically determined IC50 values showed that myricetin, quercetin, and epicatechin were the most potent inhibitors. The results also revealed that the inhibition of vanillin oxidation by flavonoids was stronger than that of phenanthridine oxidation (an N-heterocyclic substrate) as reported previously. In order to investigate the important structural features responsible for the inhibitory effects of the studied flavonoids, a quantitative structure-activity relationship (QSAR) analysis was performed. This study showed that the size of the flavonoids was the most important factor inversely affecting their potencies. The QSAR model can be used more broadly to predict the AO inhibitory activity of flavonoid-like structures for application in food-drug and drug-drug interaction studies.

Extraction, partial purification and characterisation of vanillic acid decarboxylase fromAlicyclobacillus acidoterrestrisDSM 3923

“…When the concentration increased to 1.0 mmol L −1 , VAD activity was completely inhibited by cinnamic acid, ferulic acid, resveratrol, quercetin and rutin. Polyphenols, especially flavonoids, were described to inhibit numerous unrelated enzymes . The inhibition mechanism may be due to the binding of these molecules to enzymes through hydrogen bonding, hydrophobic interactions, metal chelation and ππ ‐stacking …”

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

“…The size of flavonoids plays an important role for the AOX inhibitory effect, that is, smaller the size higher the inhibitory activity. The presence of bulkier groups and sugar units in the flavonoids lead to the reduction of AOX inhibitory activity . In 2015, Bahadori et al.…”

“…The same research group assessed the activity of 15 flavonoids spectrophotometrically and determined that myricetin, epicatechin, and quercetin are the potent AOX inhibitors. Consequently, they prepared a QSAR model to predict the activity for the broad range of flavonoids . Recently, Lepri et al.…”

“…The presence of bulkier groups and sugar units in the flavonoids lead to the reduction of AOX inhibitory activity. 241 In spathulenol, linalool, and trans-caryophyllene. Essential oil showed potent AOX inhibition with an IC 50 value of 40 g/mL.…”

“…Consequently, they prepared a QSAR model to predict the activity for the broad range of flavonoids. 241…”