Structure and ligand based drug design strategies in the development of novel 5- LOX inhibitors.
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.
National Institute of Animal Biotechnology, Hyderabad, India.
Polamarasetty
P
Aparoy
Kakularam Kumar
KK
Reddy
Pallu
P
Reddanna
D001249:Asthma / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D008024:Ligands; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D058945:Lipoxygenases / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship
D008024:Ligands; D016859:Lipoxygenase Inhibitors; D058945:Lipoxygenases