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:National Institute of Animal Biotechnology, Hyderabad, India
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.
