Miconidin acetate, a natural 5-lipoxygenase (5-LOX) inhibitor from Eugenia hiemalis Camb. (Myrtaceae)

Eugenia hiemalis grows as a tree in South America [1]. Previous studies showed primin is present in its leaves [2] and inhibits both COX-2 and 5-LOX [3]. 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) [4] was pursued using the publicly available SEA search tool [5]. Among the predicted targets, 5-LOX is linked to inflammation. MA was evaluated for 5-LOX inhibition in vitro using a cell-based assay [3] 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) [6] 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).