Abstract
Sorbitol dehydrogenase (SDH) is the second enzyme in the polyol pathway of glucose metabolism and is a possible target for the treatment of the complications of diabetes. In this study the molecular modelling program DOCK was used to analyse 249,071 compounds from the National Cancer Institute Database and predict those with high affinity for SDH. From a total of 21 tested the 7 compounds including flavin adenine dinucleotide disodium hydrate, (+)- Amethopterin, 3-hydroxy-2-napthoic(2-hydroxybenzylidene) hydrazide, folic acid, N-2,4-dinitrophenyl-L-cysteic acid, Vanillin azine and 1H-indole-2,3-dione,5-bromo-6-nitro-1-(2,3,4-tri-O-acetyl-α-L-arabinopyranosyl)-(9Cl), were shown to inhibit SDH and displayed IC50 values of 0.192 μM, 1.1 μM, 1.2 μM, 4.5 μM, 5.3 μM, 7 μM and 28 μM, respectively. These compounds may aid the design of pharmaceutical agents for the treatment of diabetes complications.
Keywords: SDH inhibitor, Zn atom, NCI database, spectrophotometer, DOCK program
Medicinal Chemistry
Title: Discovery of Potential Sorbitol Dehydrogenase Inhibitors from Virtual Screening
Volume: 2 Issue: 3
Author(s): Ossama El-Kabbani, Deborah A. Carper, Takeshi Iwata and Connie Darmanin
Affiliation:
Keywords: SDH inhibitor, Zn atom, NCI database, spectrophotometer, DOCK program
Abstract: Sorbitol dehydrogenase (SDH) is the second enzyme in the polyol pathway of glucose metabolism and is a possible target for the treatment of the complications of diabetes. In this study the molecular modelling program DOCK was used to analyse 249,071 compounds from the National Cancer Institute Database and predict those with high affinity for SDH. From a total of 21 tested the 7 compounds including flavin adenine dinucleotide disodium hydrate, (+)- Amethopterin, 3-hydroxy-2-napthoic(2-hydroxybenzylidene) hydrazide, folic acid, N-2,4-dinitrophenyl-L-cysteic acid, Vanillin azine and 1H-indole-2,3-dione,5-bromo-6-nitro-1-(2,3,4-tri-O-acetyl-α-L-arabinopyranosyl)-(9Cl), were shown to inhibit SDH and displayed IC50 values of 0.192 μM, 1.1 μM, 1.2 μM, 4.5 μM, 5.3 μM, 7 μM and 28 μM, respectively. These compounds may aid the design of pharmaceutical agents for the treatment of diabetes complications.
Export Options
About this article
Cite this article as:
El-Kabbani Ossama, Carper A. Deborah, Iwata Takeshi and Darmanin Connie, Discovery of Potential Sorbitol Dehydrogenase Inhibitors from Virtual Screening, Medicinal Chemistry 2006; 2 (3) . https://dx.doi.org/10.2174/157340606776930772
DOI https://dx.doi.org/10.2174/157340606776930772 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
Patents Relating to the Application of Autologous Bone Marrow-Derived Mesenchymal Stromal Cell and Whole Marrow Transplantation for Neurodegenerative Diseases: A Review
Recent Patents on Regenerative Medicine Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication
Anti-Cancer Agents in Medicinal Chemistry Mutations of mtDNA in some Vascular and Metabolic Diseases
Current Pharmaceutical Design mGluRI Targets Microglial Activation and Selectively Prevents Neuronal Cell Engulfment Through Akt and Caspase Dependent Pathways
Current Neurovascular Research Diabetes, Cognitive Function, and the Blood-Brain Barrier
Current Pharmaceutical Design Zinc and Type 2 Diabetes Mellitus with Periodontitis- A Systematic Review
Current Diabetes Reviews Insulin Therapy for Improving Cardiac Surgical Outcomes
Current Drug Targets The Molecular Basis of Memantine Action in Alzheimers Disease and Other Neurologic Disorders: Low-affinity, Uncompetitive Antagonism
Current Alzheimer Research Is Human Immunodeficiency Virus-Mediated Dementia an Autophagic Defect that Leads to Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Epigenomic Approach in Understanding Alzheimer’s Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Current Advances on Different Kinases Involved in Tau Phosphorylation, and Implications in Alzheimers Disease and Tauopathies
Current Alzheimer Research Nutrapharmacology of Tocotrienols for Metabolic Syndrome
Current Pharmaceutical Design A Novel Physico-Chemical Property Based Model for Studying the Effects of Mutation on the Aggregation of Peptides
Protein & Peptide Letters Biosynthesis of Flavin Cofactors in Man: Implications in Health and Disease
Current Pharmaceutical Design Metabolic Syndrome - Risk Factors for Atherosclerosis and Diabetes
Current Diabetes Reviews Basic and Clinical Aspects of Gene Therapy for Retinopathy Induced by Diabetes
Current Gene Therapy Silymarin Extends Lifespan and Reduces Proteotoxicity in C. elegans Alzheimer’s Model
CNS & Neurological Disorders - Drug Targets Editorial
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Insights into the Structure, Function, and Regulation of Human Cytochrome P450 1A2
Current Drug Metabolism Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases
CNS & Neurological Disorders - Drug Targets