LOX1 inhibition with small molecules

• LOX1 inhibition is explored through a pharmacophore approach.
• A structure-based pharmacophore model is generated and evaluated.
• The pharmacophore successfully discriminates active from inactive molecules.

Lipoxygenases (LOXs) are nonheme, iron-containing dioxygenases that catalyze the dioxygenation of polyunsaturated fatty acids and are widely distributed among plant and animal species. Human LOXs, now identified as key enzymes in the pathogenesis of major disorders, have increasingly drawn the attention as targets and great effort has been made for the discovery and design of suitable inhibitors, to which end both pharmacological and computational methods have been employed. In the present work, using pharmacophore modeling and docking, we attempt to elucidate the inhibition of LOX1 with a new inhibitor, albidoside, an iridoid glucoside isolated from plants of the Scutellaria genus. Through a pharmacophore approach, complementarities between the ligand and the binding site are explored and a plausible mode of binding with the protein is suggested for albidoside.

Figure optionsDownload high-quality image (150 K)Download as PowerPoint slide