Title:Resorcinol Derivatives as Novel Aldose Reductase Inhibitors: In Silico and
In Vitro Evaluation
Volume: 19
Issue: 9
Author(s): Namık Kılınç*
Affiliation:
- Department of Medical Services and Techniques, Vocational School of Health Service, Igdir University, Igdir, Turkey
Keywords:
Aldose reductase, Resorcinol derivatives, molecular docking, diabetic complications, polyol pathway, ADME.
Abstract:
Background: The polyol pathway, an alternative way of carbohydrate metabolism, is activated
by hyperglycemia. Aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, is
responsible for the reduction of glucose to sorbitol. Inhibiting the aldose reductase enzyme and reducing
the polyol pathway is considered an effective method to prevent and postpone the onset of diabetic complications.
Objective: Therefore, in this work, we investigate the inhibition effects of certain resorcinol derivatives
and the positive control compound quercetin on the AR enzyme in vitro and in silico. These phenolic
compounds, whose inhibitory effects on the AR enzyme were investigated, were also compared with
known drugs in terms of their drug-like characteristics.
Methods: Three methods were used to determine the inhibitory effects of resorcinol derivatives on recombinant
human AR enzyme. After the in vitro inhibition effects were determined spectrophotometrically,
the binding energy and binding modes were determined by molecular docking method. Finally, the
MM-GBSA method was used to determine the free binding energies of the inhibitors for the AR enzyme.
Results: 5-pentylresorcinol compound showed the strongest inhibition effect on recombinant human AR
enzyme with an IC50 value of 9.90 μM. The IC50 values of resorcinol, 5-methylresorcinol, 4-
ethylresorcinol, 4-hexylresorcinol, 2-methylresorcinol, and 2,5-dimethylresorcinol compounds were determined
as 49.50 μM, 43.31 μM, 19.25 μM, 17.32 μM, 28.87 μM, 57.75 μM, respectively.
Conclusion: The results of this research showed that resorcinol compounds are effective AR inhibitors.
These findings are supported by molecular docking, molecular mechanics, and ADME investigations
undertaken to corroborate the experimental in vitro results.
