Abstract
Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5- HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma.
In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors.
Keywords: Arachidonic acid, 5-LOX, asthma, drug design, pharmacophore, QSAR, scaffold hopping, pseudoreceptor
Current Medicinal Chemistry
Title:Structure and Ligand Based Drug Design Strategies in the Development of Novel 5- LOX Inhibitors
Volume: 19 Issue: 22
Author(s): Polamarasetty Aparoy, Kakularam Kumar Reddy and Pallu Reddanna
Affiliation:
Keywords: Arachidonic acid, 5-LOX, asthma, drug design, pharmacophore, QSAR, scaffold hopping, pseudoreceptor
Abstract: Lipoxygenases (LOXs) are non-heme iron containing dioxygenases involved in the oxygenation of polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA). Depending on the position of insertion of oxygen, LOXs are classified into 5-, 8-, 9-, 12- and 15-LOX. Among these, 5-LOX is the most predominant isoform associated with the formation of 5-hydroperoxyeicosatetraenoic acid (5- HpETE), the precursor of non-peptido (LTB4) and peptido (LTC4, LTD4, and LTE4) leukotrienes. LTs are involved in inflammatory and allergic diseases like asthma, ulcerative colitis, rhinitis and also in cancer. Consequently 5-LOX has become target for the development of therapeutic molecules for treatment of various inflammatory disorders. Zileuton is one such inhibitor of 5-LOX approved for the treatment of asthma.
In the recent times, computer aided drug design (CADD) strategies have been applied successfully in drug development processes. A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article. Since the crystal structure of 5-LOX has been recently solved, efforts to develop 5-LOX inhibitors have mostly relied on ligand based rational approaches. The present review provides a comprehensive survey on these strategies in the development of 5-LOX inhibitors.
Export Options
About this article
Cite this article as:
Aparoy Polamarasetty, Kumar Reddy Kakularam and Reddanna Pallu, Structure and Ligand Based Drug Design Strategies in the Development of Novel 5- LOX Inhibitors, Current Medicinal Chemistry 2012; 19 (22) . https://dx.doi.org/10.2174/092986712801661112
DOI https://dx.doi.org/10.2174/092986712801661112 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Inflammation, Hyperinflammation & Cystic Fibrosis Lung Disease – A Paradigm Shift?
Current Respiratory Medicine Reviews The Long and Winding Road: Searching for Non-MHC Psoriasis Susceptibility Loci
Current Genomics Novel Delivery Systems for Anti-Allergic Agents: Allergic Disease and Innovative Treatments
Current Drug Delivery The 5-lipoxygenase (5-LOX) Inhibitor Zileuton Reduces Inflammation and Infarct Size with Improvement in Neurological Outcome Following Cerebral Ischemia
Current Neurovascular Research Histone Deacetylase Inhibitors in Psoriasis Therapy
Current Drug Targets - Inflammation & Allergy Biological Importance of a Biflavonoid ‘Bilobetin’ in the Medicine: Medicinal Importance, Pharmacological Activities and Analytical Aspects
Infectious Disorders - Drug Targets One-pot Synthesis and its Practical Application in Pharmaceutical Industry
Current Organic Synthesis Asthma, Airway Smooth Muscle Cell, and Bronchial Thermoplasty
Current Respiratory Medicine Reviews Oral Agents in Multiple Sclerosis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Anti-Inflammatory Effects of Triterpenoids; Naturally Occurring and Synthetic Agents
Mini-Reviews in Organic Chemistry Air Pollution and Lung Cancer
Current Respiratory Medicine Reviews CD28: A New Drug Target for Immune Disease
Current Drug Targets Optimization of Time Controlled 6-mercaptopurine Delivery for Site- Specific Targeting to Colon Diseases
Current Drug Delivery Autophagy Modulators and Neuroinflammation
Current Medicinal Chemistry Should We Develop an Inhaled Anti-pneumococcal Vaccine for Adults?
Current Medicinal Chemistry - Anti-Infective Agents Beta-Blockers: Current State of Knowledge and Perspectives
Mini-Reviews in Medicinal Chemistry Recent Advances in Liver X Receptor Biology and Chemistry
Current Topics in Medicinal Chemistry Editorial [Hot Topic:Therapeutic Potential of Peptide Motifs - Part V (Executive Guest Editor: Jean-Claude Herve)]
Current Pharmaceutical Design Acute Effects of Passive Smoking on Asthma in Childhood
Inflammation & Allergy - Drug Targets (Discontinued) Formulation Development and Characterization of Guar Gum Microspheres for Colon Delivery
Nanoscience & Nanotechnology-Asia