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 <i>Eugenia hiemalis</i> 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 % <i>in vitro</i> 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 <i>in silico</i> 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 <i>E. hiemalis</i> are an interesting source of anti-inflammatory compounds, mainly of miconidin acetate.