In silico identification of novel leukotriene A4 hydrolase inhibitors as potential anti-inflammatory agents

Abstract EN

Leukotriene A4 Hydrolase (LTA4H) is considered an indispensable enzyme in the cascade of producing inflammatory mediators.

Overproducing inflammatory mediators will end with inflammatory diseases that are disturbing to the patient.

Selective inhibition of this enzyme will alleviate the symptoms of inflammation and promote the patient’s lifestyle.

Within this study, a solitary 3D structure-based pharmacophore has been constructed for this enzyme that contains a distinguished “Zinc Binding Feature” that selectively extracts candidate inhibitors which contain functional groups that coordinate with zinc atom, a property that increases selectivity and affinity for this enzyme.

The selection process for potential inhibitors was performed by screening commercially available AldrichCPR over the generated pharmacophore combined with advanced docking procedures.

Twelve compounds were introduced to be potential inhibitors containing different functional groups and all are possessing drug likeness properties.