Abstract
Background: The glyoxylate shunt of fatty acid metabolism is critical to the survival of Mycobacterium tuberculosis (Mtb) during the dormant stage. The two enzymes of glyoxylate shunt pathway, isocitrate lyase (ICL) and malate synthase (MS), have been identified to be involved in Mtb persistence and become the attractive targets to intervene with the pathway.
Methods: In order to search novel MS inhibitors, molecular docking in autodock Vina was employed for the first time to virtually screen Fragment-Like subset of ZINC database against MS crystal structure.
Results: Total 11 candidates were screened out based on binding score, binding conformation, and structural diversity.
Conclusion: The interaction mode analysis, binding affinity reassessment and ADME predictions of these candidates indicate they all can be treated as potential MS inhibitors. Their skeletons can be classified into four novel types, i.e., pyrrolo[3,4-d]pyrimidine, chromen-2-one, hetero biphenyl and phenyl substituted chiral cyclic diketone, which will bring an encouraging enlightenment to enrich the category of MS inhibitors and broaden their research scope.
Keywords: AutoDock Vina, inhibitor, malate synthase, molecular docking, tuberculosis, virtual screening.
Current Enzyme Inhibition
Title:Four Types of Novel Potential Malate Synthase Inhibitors from Virtual Screening
Volume: 13 Issue: 3
Author(s): Ming-Liang Chang, Yong He, Chuan Zhao, Lan-Fang Hao and Shao-Yong Li*
Affiliation:
- Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Basic Medical Research Center, Tianjin Medical University, Tianjin 300070,China
Keywords: AutoDock Vina, inhibitor, malate synthase, molecular docking, tuberculosis, virtual screening.
Abstract: Background: The glyoxylate shunt of fatty acid metabolism is critical to the survival of Mycobacterium tuberculosis (Mtb) during the dormant stage. The two enzymes of glyoxylate shunt pathway, isocitrate lyase (ICL) and malate synthase (MS), have been identified to be involved in Mtb persistence and become the attractive targets to intervene with the pathway.
Methods: In order to search novel MS inhibitors, molecular docking in autodock Vina was employed for the first time to virtually screen Fragment-Like subset of ZINC database against MS crystal structure.
Results: Total 11 candidates were screened out based on binding score, binding conformation, and structural diversity.
Conclusion: The interaction mode analysis, binding affinity reassessment and ADME predictions of these candidates indicate they all can be treated as potential MS inhibitors. Their skeletons can be classified into four novel types, i.e., pyrrolo[3,4-d]pyrimidine, chromen-2-one, hetero biphenyl and phenyl substituted chiral cyclic diketone, which will bring an encouraging enlightenment to enrich the category of MS inhibitors and broaden their research scope.
Export Options
About this article
Cite this article as:
Chang Ming-Liang, He Yong, Zhao Chuan, Hao Lan-Fang and Li Shao-Yong*, Four Types of Novel Potential Malate Synthase Inhibitors from Virtual Screening, Current Enzyme Inhibition 2017; 13 (3) . https://dx.doi.org/10.2174/1573408013666161110124925
DOI https://dx.doi.org/10.2174/1573408013666161110124925 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
![](/images/wayfinder.jpg)
- 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
-
Danger-Detector NKG2D: Immunosurveillance of Induced Self and Modulation by Cytokines and Soluble Ligands
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Marine Products with Anti-Protozoal Activity: A Review
Current Clinical Pharmacology Therapeutic Modulation of Cytokines in Chronic Infectious Diseases
Current Pharmaceutical Design Ethambutol Induced Lichenoid Drug Eruption: A Case Report
Current Drug Safety Electrochemical Biosensor for the Detection of Amygdalin in Apple Seeds with a Hybrid of f-MWCNTs/CoFe2O4 Nanocomposite
Current Analytical Chemistry Current and Future Pharmaceutical Therapy for Rheumatoid Arthritis
Current Pharmaceutical Design Dihydrofolate Reductase as a Model for Enzyme Catalysis
Current Biotechnology Anomalous Vascular Supply of Bronchial Circulation in Cystic Fibrosis Patients with Massive Hemoptysis
Current Respiratory Medicine Reviews Platensimycin: A Promising Antimicrobial Targeting Fatty Acid Synthesis
Current Medicinal Chemistry Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Concepts
Current Drug Safety Analysis of Capsaicinoids in Hot Sauces Using a Silica Hydride-Based Stationary Phase
Current Chromatography The Current Chemical Utility of Marine and Terrestrial Filamentous Fungi in Side-Chain Chemistry
Current Organic Chemistry Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Synthesis of Coumarin-benzotriazole Hybrids and Evaluation of their Anti-tubercular Activity
Letters in Organic Chemistry New Insights into Vitamin D and Autophagy in Inflammatory Bowel Diseases
Current Medicinal Chemistry Novel, Unifying Phagomimetic Mechanism of Vancomycin Therapeutic Action and Toxicity: Polyphenol, Electron Transfer and Reactive Oxygen Species
Anti-Infective Agents in Medicinal Chemistry <i>Enoyl-Acyl Carrier Protein Reductase (INHA)</i>: A Remarkable Target to Exterminate Tuberculosis
Anti-Infective Agents Hepatitis C Viruss Immune Evasion Strategies
Current Immunology Reviews (Discontinued) Inflammasome Signaling in Pathogenesis of Lung Diseases
Current Pharmaceutical Design A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities
Current Topics in Medicinal Chemistry