Eicosanoids, oxymetabolites of arachidonic acid (AA) formed via Cyclooxygenase (COX) and Lipoxygenase (LOX) pathways, play an important role in the regulation of physiological and pathological processes. Development of mono/dual/multi enzyme specific inhibitors, for achieving optimum therapeutic efficacy and safety, is the need of the hour and is a challenging task. In our study, AA binding site in COXs (COX-1 and COX-2) and LOXs (5-LOX, 12-LOX, 15-LOX) were compared by the development of receptor based pharmacophores in various combinations. It has been identified that aliphatic and aromatic interactions are the most common. In addition, interactions unique and common to various enzymes were identified. The insights obtained were validated by docking studies with existing specific COX-2 inhibitor (celecoxib), 5-LOX inhibitor (ABT-761), COX-2/5-LOX dual inhibitor (Licofelone) and 5-LOX/12-LOX/15-LOX inhibitor (BW75C).Structure based drug design strategies were further employed to propose 5-LOX specific and COX-2/5-LOX dual inhibitors.

Exploration of binding site pattern in arachidonic acid metabolizing enzymes and the design of specific and dual/multi enzyme inhibitors

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.