Miconidin Acetate and Primin as Potent 5-Lipoxygenase Inhibitors from Brazilian Eugenia hiemalis (Myrtaceae)

Abstract

This paper describes the isolation and identification of primin and miconidin acetate as metabolites from the flower bud extract of Eugenia hiemalis as well as the anti-inflammatory activity of miconidin acetate by inhibition of 5-lipoxygenase. Miconidin acetate inhibited leukotriene B4 formation catalyzed by the human recombinant enzyme (IC50 = 0.3 ± 0.17 µM) more than primin (IC50 = 1.4 ± 0.6 µM) and zileuton (IC50 = 1.1 ± 0.7 µM). Miconidin acetate (20 µM) inhibited LTB4 formation to an extent of 59 ± 12 % in vitro using a cell-based assay, comparable to the positive control zileuton (69 ± 12 % inhibition at a concentration of 10 µM). The binding modes of miconidin acetate were further evaluated in silico by molecular docking to the human 5-lipoxygenase crystal structure. The hydroxyl group was predicted to form a hydrogen bond with the terminal Ile676, while the pentyl moiety occupied the hydrophobic substrate channel. The obtained results show that flower buds of E. hiemalis are an interesting source of anti-inflammatory compounds, mainly of miconidin acetate.