Molecular Docking Evaluation of Some Natural Phenolic Compounds as Aldose Reductase Inhibitors for Diabetic Complications
Open Access
- 2 November 2017
- journal article
- Published by Chitkara University Publications in Journal of Pharmaceutical Technology, Research and Management
- Vol. 5 (2), 135-148
- https://doi.org/10.15415/jptrm.2017.52009
Abstract
The enzyme aldose reductase (AR) is a member of aldoketoreductase super-family which catalyzes the formation of sorbitol from glucose through polyol pathway of glucose catabolism. Reduced sorbitol production via polyol pathway due to AR inhibition is a target of choice for controlling major complications of diabetes. Epalrestat is the only commercially available inhibitor of AR till date,thus, there is a great need to search for more economical, nontoxic and safer inhibitors of AR enzyme. Flavonoids, the polyphenol compounds in plants have been reported for inhibitory effects against AR. The objective of this study is to explore the binding modes of natural phenolic compounds with AR to design safer natural drugs as alternatives to synthetic drugs. We conducted a molecular docking study on some natural phenolic compounds with AR enzyme in complex with the synthetic inhibitor. The overlay of the docked pose of the selected natural phenols with the ARreference inhibitor complex showed that the selected natural compounds have the similar binding pattern with the active site residues of the enzyme as that of co-crystallized inhibitor. The results of docking study showed the best binding affinity of AR with that of 2-(4-hydroxy-3-methoxyphenyl) ethanoic acid and butein, having the lowest binding free energy of –9.8 kcal/mol and–9.7 kcal/mol, respectively. This information can be utilized to design potent, economical and non-toxic natural AR inhibitors from natural phenols for the therapeutics of diabetic complications.Keywords
This publication has 32 references indexed in Scilit:
- Expanding role of the Madras Diabetes Research Foundation - Indian Diabetes Risk Score in clinical practiceIndian Journal of Endocrinology and Metabolism, 2013
- Type 2 Diabetes Mellitus: A Review of Current TrendsOman Medical Journal, 2012
- Frog2: Efficient 3D conformation ensemble generator for small compoundsNucleic Acids Research, 2010
- Inhibition of aldose reductase by dietary antioxidant curcumin: Mechanism of inhibition, specificity and significanceFEBS Letters, 2009
- AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibilityJournal of Computational Chemistry, 2009
- Diabetes-Related Microvascular and Macrovascular Diseases in the Physical Therapy SettingPTJ: Physical Therapy & Rehabilitation Journal, 2008
- Biochemistry and molecular cell biology of diabetic complicationsNature, 2001
- The Protein Data BankNucleic Acids Research, 2000
- Effect of Polygonum hydropiper Sulfated Flavonoids on Lens Aldose Reductase and Related EnzymesJournal of Natural Products, 1996
- Search for Naturally Occurring Substances to Prevent the Complications of Diabetes. II. Inhibitory Effect of Coumarin and Flavonoid Derivatives on Bovine Lens Aldose Reductase and Rabbit Platelet Aggregation.CHEMICAL & PHARMACEUTICAL BULLETIN, 1995