Abstract
Background: Cholesterol, derived from two different sources of endogenous synthesis and diet, is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann- Pick C1-like 1 (NPC1L1).
Objective: The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening.
Conclusion: Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose novel cholesterol absorption inhibitors.
Keywords: Cholesterol absorption inhibitors, ezetimibe, NPC1L1, virtual screening.
Medicinal Chemistry
Title:Virtual Screening for Cholesterol Absorption Inhibitors
Volume: 11 Issue: 1
Author(s): Lidan Sun, Hai Qian and Wenlong Huang
Affiliation:
Keywords: Cholesterol absorption inhibitors, ezetimibe, NPC1L1, virtual screening.
Abstract: Background: Cholesterol, derived from two different sources of endogenous synthesis and diet, is essential for the growth and maintenance of mammalian cells. However, elevated level of serum cholesterol is among the associated risk factors for the coronary heart disease. Statins can reduce endogenous sterol synthesis by inhibiting HMG-CoA reductase, whereas cholesterol absorption inhibitors, such as ezetimibe, can block cholesterol uptake from dietary sources by blocking Niemann- Pick C1-like 1 (NPC1L1).
Objective: The present review focuses on the main research progress of cholesterol absorption inhibitors, the structure of NPC1L1 and discovery of novel chemical entities by virtual screening.
Conclusion: Studies on the structure-activity relationship reveal that azetidinone is important to maintain activity in azetidinone derivatives and the novel heterocyclic compounds with replacement of β-lactam scaffold by oxazolidinone also show similar activity as ezetimibe. Moreover, virtual screening is a computer-aided molecular design tool to propose novel cholesterol absorption inhibitors.
Export Options
About this article
Cite this article as:
Sun Lidan, Qian Hai and Huang Wenlong, Virtual Screening for Cholesterol Absorption Inhibitors, Medicinal Chemistry 2015; 11 (1) . https://dx.doi.org/10.2174/1573406410666140428152436
DOI https://dx.doi.org/10.2174/1573406410666140428152436 |
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
-
New Insights into the Pleiotropic Effects of Statins for Stroke Prevention
Mini-Reviews in Medicinal Chemistry The Impact of Dietary Habits and Nutritional Deficiencies in Urban African Patients Living with Heart Failure in Soweto, South Africa – A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Is there a Role for Cortisol in the Accumulation of Lipids in the Intima a Crucial Step of Atherogenesis?
Current Vascular Pharmacology Statin Treatment and the Natural History of Atherosclerotic-Related Diseases: Pathogenic Mechanisms and the Risk-Benefit Profile
Current Pharmaceutical Design Peripartum Cardiomyopathy: Moving Towards a More Central Role of Genetics
Current Cardiology Reviews Effects of Statins on Bone Markers, Bone Mineral Density and Fractures. Possible Role in Osteoporosis Treatment
Current Pharmaceutical Analysis Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics
Current Protein & Peptide Science Marine Algae As A Prospective Source For Antidiabetic Compounds – A Brief Review
Current Diabetes Reviews Ventricular Arrhythmias in Patients with Obstructive Sleep Apnea
Current Cardiology Reviews 1, 2-Benzisoxazole: A Privileged Structure with a Potential for Polypharmacology
Current Pharmaceutical Design Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible Diabetes (ATTEMPT): A Prospective-Randomized Study in Middle Aged Men and Women
Current Vascular Pharmacology Editorial (Thematic Issue: Current Therapeutic Options in Cardiomyopathies)
Current Pharmaceutical Design Patent Selections
Recent Patents on Cardiovascular Drug Discovery Overview of Coumarins and its Derivatives: Synthesis and Biological Activity
Letters in Organic Chemistry Synthesis, Characterization and Evaluation of Gemfibrozil-Stilbene Hybrid as Antioxidant Agent
Letters in Drug Design & Discovery Statistical monitoring-based alarming systems in modeling the AIDS epidemic in the United States, 1985-2011
Current HIV Research Transmucosal Delivery of Linagliptin for the Treatment of Type- 2 Diabetes Mellitus by Ultra-Thin Nanofibers
Current Drug Delivery The Etiology of Hypertension in the Metabolic Syndrome Part Two: The Gene-Environment Interaction
Current Vascular Pharmacology Pharmacotherapies to Manage Bone Loss-Associated Diseases: A Quest for the Perfect Benefit-to-Risk Ratio
Current Medicinal Chemistry Impact of COX-2 Inhibitors in Common Clinical Practice a Gastroenterologists Perspective
Current Topics in Medicinal Chemistry