Abstract
It has long been recognised that high circulating levels of cholesterol are associated with the development of cardiovascular disease. With the discovery of the cholesterol biosynthetic pathway in 1950, it was soon realised that blockade of key conversions in this pathway may provide useful therapeutic targets for the management of hypercholesterolaemia. In the 1970s the first useful inhibitors of cholesterol biosynthesis were isolated, and paved the way for what would become a multimillion dollar pharmaceutical industry. Modern-day statins are incredibly effective hypolipidaemic agents, interrupting cholesterol biosynthesis at the rate-limiting step through a competitive inhibition mechanism. These compounds’ structures interact with key amino acid residues through a variety of defined bonding interactions, and by understanding how these interactions form, better, and safer, hypolipidaemic agents were found. This review describes the historical development of statins and brings us up-to-date with current structure-activity relationships between statins and their target enzyme.
Keywords: Cardiovascular disease, Cholesterol, HMG-CoA reductase, Hypercholesterolaemia, Lipoproteins.
Mini-Reviews in Medicinal Chemistry
Title:From fungus to pharmaceuticals – the chemistry of statins
Volume: 12 Issue: 12
Author(s): P.A.C. McPherson
Affiliation:
Keywords: Cardiovascular disease, Cholesterol, HMG-CoA reductase, Hypercholesterolaemia, Lipoproteins.
Abstract: It has long been recognised that high circulating levels of cholesterol are associated with the development of cardiovascular disease. With the discovery of the cholesterol biosynthetic pathway in 1950, it was soon realised that blockade of key conversions in this pathway may provide useful therapeutic targets for the management of hypercholesterolaemia. In the 1970s the first useful inhibitors of cholesterol biosynthesis were isolated, and paved the way for what would become a multimillion dollar pharmaceutical industry. Modern-day statins are incredibly effective hypolipidaemic agents, interrupting cholesterol biosynthesis at the rate-limiting step through a competitive inhibition mechanism. These compounds’ structures interact with key amino acid residues through a variety of defined bonding interactions, and by understanding how these interactions form, better, and safer, hypolipidaemic agents were found. This review describes the historical development of statins and brings us up-to-date with current structure-activity relationships between statins and their target enzyme.
Export Options
About this article
Cite this article as:
McPherson P.A.C., From fungus to pharmaceuticals – the chemistry of statins, Mini-Reviews in Medicinal Chemistry 2012; 12 (12) . https://dx.doi.org/10.2174/138955712802762103
DOI https://dx.doi.org/10.2174/138955712802762103 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
Preventing Type 2 Diabetes Mellitus: Room for Residual Risk Reduction After Lifestyle Changes?
Current Pharmaceutical Design Effects of Exercise on Anxiety and Depression Disorders: Review of Meta- Analyses and Neurobiological Mechanisms
CNS & Neurological Disorders - Drug Targets Bioprocess and Bioreactor: Next Generation Technology for Production of Potential Plant-based Antidiabetic and Antioxidant Molecules
Current Medicinal Chemistry Genesis of Dihydropyrimidinone Calcium Channel Blockers: Recent Progress in Structure-Activity Relationships and Other Effects
Mini-Reviews in Medicinal Chemistry P2X Receptors in the Cardiovascular System and their Potential as Therapeutic Targets in Disease
Current Medicinal Chemistry Beta-Blockers as First Line Treatment of Hypertension: A Proponents View
Current Hypertension Reviews Editorial (Hot Topic: Novel Biomarkers in the Prognosis, Progression and Treatment of Cardiovascular Disease: The Role of microRNAs )
Current Topics in Medicinal Chemistry Dynamics of Telomere Length in Different Age Groups in a Latvian Population
Current Aging Science Knowing is Half the Battle: Targeting Virulence Factors of Group A Streptococcus for Vaccine and Therapeutics
Current Drug Targets Type 2 Diabetes Mellitus and the Elderly: An Update on Drugs Used to Treat Glycaemia
Current Vascular Pharmacology Rosuvastatin, Pravastatin, and Atorvastatin for the Treatment of Hypercholesterolaemia in HIV-Infected Patients Receiving Protease Inhibitors
Current HIV Research Structure-to-function Relationship of Carbohydrates in the Mechanism of Lysosomal Storage Disorders (LSDs)
Current Organic Chemistry SIRT1 as a Promising Novel Therapeutic Target for Myocardial Ischemia Reperfusion Injury and Cardiometabolic Disease
Current Drug Targets Does Erythropoietin Always Win?
Current Medicinal Chemistry Macrophage Differentiation to Foam Cells
Current Pharmaceutical Design Resveratrol and Its Analogues: Promising Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Opportunities and Challenges in Nano-structure Mediated Drug Delivery: Where Do We Stand?
Current Nanomedicine 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors as Promising Therapeutic Drugs for Diabetes: Status and Development
Current Medicinal Chemistry Refined Purification of Large Amounts of Rat cvHsp/HspB7 and Partial Biological Characterization In Vitro
Protein & Peptide Letters Regulatory Mechanisms of Cardiac Development and Repair
Cardiovascular & Hematological Disorders-Drug Targets