Evaluation of Pharmacokinetic Parameters, Toxicity, and Molecular Docking of Flavonols with Aldose Reductase Enzyme to Find an Effective Compound in Inhibition of this Enzyme

Aldose reductase plays an important role in chronic diabetes and can cause tissue complications. Controlling the activity of aldose reductase provides an important strategy in controlling the complications of diabetes. Flavonoids are important inhibitors of aldose reductase. This study aimed to investigate the inhibitory nature of flavonol compounds in fruits and plants on aldose reductase activity by bioinformatic methods.

This study was descriptive-analytical. First, the structure of flavonol compounds, Ranirestat, and enzymes were downloaded from ChemSpider and PDB databases, respectively. Ranirestat was used as the standard drug. The pharmacokinetic properties and toxicity of the compounds were predicted by Swiss ADME, Protox servers, and Toxtree2.5.4 software. Then, to interact the compounds with the enzyme structure, molecular docking was used to method AutoDock Tools 1.5.6. Finally, the results were analyzed using Discovery Studio 3.5 software.

The results showed that all flavonol compounds were desirable in pharmacokinetic properties and lacked toxicity. All compounds were able to inhibit aldose reductase enzymes with different PDB codes. However, among these compounds, the combination of Rutin with average docking energy of 191.21 kcal/ mole (P-value <0.05) had stronger binding energy than the standard Ranirestat drug.

From the results of this study, it can be concluded that among the selected flavonol compounds, the Rutin compound showed stronger inhibitory activity than other flavonol compounds due to its interaction with important amino acids in the active site of the enzyme. As a result, further study of this compound in vivo and in vitro environments can be used as a potential candidate to inhibit the enzyme aldose reductase and ultimately prevent chronic complications of diabetes.