Abstract
Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase or some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated by three histidines is a bifunctional enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson’s disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin 283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41 A, respectively, through its O5 atom.
Keywords: Ascorbic acid, in silico, in vitro, molecular docking, tyrosinase inhibition, vitamin C.
Current Topics in Medicinal Chemistry
Title:In Silico Approach to Inhibition of Tyrosinase by Ascorbic Acid Using Molecular Docking Simulations
Volume: 14 Issue: 12
Author(s): F. Sezer Senol, M. Tareq Hassan Khan, Gurdal Orhan, Erdem Gurkas, Ilkay Erdogan Orhan, Nese Subutay Oztekin and Fikri Ak
Affiliation:
Keywords: Ascorbic acid, in silico, in vitro, molecular docking, tyrosinase inhibition, vitamin C.
Abstract: Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase or some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated by three histidines is a bifunctional enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson’s disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin 283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41 A, respectively, through its O5 atom.
Export Options
About this article
Cite this article as:
Senol Sezer F., Khan Tareq Hassan M., Orhan Gurdal, Gurkas Erdem, Orhan Erdogan Ilkay, Oztekin Subutay Nese and Ak Fikri, In Silico Approach to Inhibition of Tyrosinase by Ascorbic Acid Using Molecular Docking Simulations, Current Topics in Medicinal Chemistry 2014; 14 (12) . https://dx.doi.org/10.2174/1568026614666140610121253
DOI https://dx.doi.org/10.2174/1568026614666140610121253 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Focus on Heme Oxygenase-1 (HO-1) Inhibitors
Current Medicinal Chemistry SKINOMICS: Transcriptional Profiling in Dermatology and Skin Biology
Current Genomics Sucrose Isomerase and Its Mutants from Erwinia rhapontici Can Synthesise α-Arbutin
Protein & Peptide Letters Treating Cancer in Older and Oldest Old Patients
Current Pharmaceutical Design Interferon: Cellular Executioner or White Knight?
Current Medicinal Chemistry siRNA Silencing of Gene Expression in Trabecular Meshwork: RhoA siRNA Reduces IOP in Mice
Current Molecular Medicine Medicinal Research Progress of Natural Coumarin and its Derivatives
The Natural Products Journal Endocrine Disruptors and Human Health
Mini-Reviews in Medicinal Chemistry Azidothymidine is Effective Against Human Multiple Myeloma: A New Use for an Old Drug?
Anti-Cancer Agents in Medicinal Chemistry Bilirubin and the Genome: The Hereditary Basis of Unconjugated Neonatal Hyperbilirubinemia
Current Pharmacogenomics Immunoliposomes: Synthesis, Structure, and their Potential as Drug Delivery Carriers
Current Cancer Therapy Reviews Evaluation of the Performance of Manganese Phthalocyanines as Superoxide Dismutase Mimics
Current Analytical Chemistry Serotonin – Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments
Current Drug Targets γ δ T Cell Modulation in Anticancer Treatment
Current Cancer Drug Targets Use of DNA Stabilizers to Extend Plasmid Biological Activity
Current Bionanotechnology (Discontinued) Biochemistry and Physiology of Anabolic Androgenic Steroids Doping
Mini-Reviews in Medicinal Chemistry Challenges in Diagnosis of Reproductive Dysfunction
Current Women`s Health Reviews Nongenomic Actions of Thyroid Hormones: Every why has a Wherefore
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Aberrant Regulation of Translation Initiation in Tumorigenesis
Current Molecular Medicine