Ligand-based Pharmacophore Modeling for Discovery of Potential 14-α-demethylase Inhibitors.

The cytochrome p450 enzyme 14-α-demethylase seems to be a potential target against Acanthamoeba keratitis. This enzyme is involved in the biosynthesis of ergosterol on the membrane of Acanthamoeba1. The Acanthamoeba is a free-living protozoan, which through an abrasion in the ocular epithelium causes Acanthamoeba keratitis. To date, there is no specific and efficacy agent to the treatment of this devastating ocular infection 2. With the aim to find new active compounds against Acanthamoeba, a ligand-based pharmacophore modeling was created. The inhibitors of the enzyme were selected carefully through the Binding Database3 and the pharmacophoric model was built by PharmaGist4 server. The best pharmacophore model shows as features an aromatic ring, a hydrogen acceptor group and positivity charge. The model created will be validated and used in silico screening of 14-α-demethylase inhibitors in order to discover a novel scaffold as agents for the treatment of Acanthamoeba keratitis.