Miconidin acetate, a natural 5-lipoxygenase (5-LOX) inhibitor from Eugenia hiemalis Camb. (Myrtaceae)
Eugenia hiemalis grows as a tree in South America . Previous studies showed primin is present in its leaves  and inhibits both COX-2 and 5-LOX . In this study, a primin-related metabolite, miconidin acetate (MA), was isolated from CH2Cl2 extract of E. hiemalis collected in Southern Brazil. In the search for protein targets mediating a possible anti-inflammatory effect of MA, a similarity ensemble approach (SEA)  was pursued using the publicly available SEA search tool . Among the predicted targets, 5-LOX is linked to inflammation. MA was evaluated for 5-LOX inhibition in vitro using a cell-based assay  and detecting LTB4 with an ELISA kit. MA (20 µM) inhibited LTB4 formation to an extent of 59 ± 12%; the positive control zileuton (10 µM) inhibited 5-LOX 69 ± 12%. MA was docked into an X-ray crystal structure (PDB entry 3o8y)  using GOLD 5.2 (CCDC, GB). The resulting poses place MA close to the catalytic iron and the OH group is predicted to form H bond with the terminal Ile676. The pentyl moiety occupies the hydrophobic substrate channel (Fig. 1).
 Reitz R, Legrand CD, Klein RM. Myrtaceae (Flora Ilustrada Catarinense). Itajaí: Herbário Barbosa Rodrigues; 1967 – 1971:487.
 Falkenberg MB. Chinone und andere Inhaltstoffe aus Eugenia hiemalis Cambessèdes und Paramyrciaria glazioviana (Kiaerskou) Sobral (Myrtaceae). PhD Thesis Universität Bonn, 1996.
 Landa P, Kutil Z, Temml V, Malik J, Kokoska L, Widowitz U, Pribylova M, Dvorakova M, Marsik P, Schuster D, Bauer R, Vanek T. Inhibition of in vitro leukotriene B4 biosynthesis in human neutrophil granulocytes and docking studies of natural quinones. Nat Prod Commun 2013; 8:105 – 108.
 Keiser MJ, Roth BL, Armbruster BN, Ernsberger P, Irwin JJ, Shoichet BK. Relating protein pharmacology by ligand chemistry. Nat Biotech 2007; 25:197 – 206.
 Gilbert NC, Bartlett SG, Waight MT, Neau DB, Boeglin WE, Brash AR, Newcomer ME. The structure of human 5-lipoxygenase. Science 2011; 14: 217 – 219.