QSAR and Docking Studies on Propenone Derivatives as Dual COX and 5- LOX Inhibitors
About: This article is published in Letters in Organic Chemistry.The article was published on 2008-09-30. It has received 2 citations till now. The article focuses on the topics: Docking (molecular).
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TL;DR: A comprehensive review on structure based drug design strategies in the development of novel 5-LOX inhibitors is presented in this article.
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.
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Cites background from "QSAR and Docking Studies on Propeno..."
...Further Mukesh Doble and his group developed QSAR model of seventeen propenone derivatives [117], which were reported to be COX-2/5LOX dual inhibitors [98]....
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TL;DR: In this article, the authors report on their quest for novel, clinically relevant inhibitors of local invasion, based on a broad screen of natural products in a phenotypic assay, starting from micromolar chalcone hits, a predictive QSAR model for diaryl propenones was developed, and synthetic analogues with a 100-fold increase in potency were obtained.
12 citations