Structure and Ligand Based Drug Design Strategies in the Development of Novel 5- LOX Inhibitors
| Autor: | Polamarasetty Aparoy, Pallu Reddanna, Kakularam Kumar Reddy |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Drug
endocrine system diseases drug design media_common.quotation_subject Quantitative Structure-Activity Relationship scaffold hopping Pharmacology Ligands Biochemistry Article chemistry.chemical_compound Neoplasms Drug Discovery medicine Humans 5-LOX Lipoxygenase Inhibitors Asthma media_common chemistry.chemical_classification pharmacophore integumentary system QSAR Ligand Chemistry Organic Chemistry food and beverages Zileuton asthma Lipoxygenases medicine.disease Arachidonic acid Drug development pseudoreceptor Molecular Medicine Structure based lipids (amino acids peptides and proteins) medicine.drug Polyunsaturated fatty acid |
| Zdroj: | Current Medicinal Chemistry |
| ISSN: | 0929-8673 |
| DOI: | 10.2174/092986712801661112 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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