Mammalian lipoxygenases (LOs) are heterogeneous families of enzymes distributed widely throughout the plant and animal kingdoms, and are responsible for the oxidation of polyunsaturated fatty acids and esters to hydroperoxy derivatives [1]. These are non-heme iron-containing enzymes and named according to the position at which a key substrate, arachidonic acid (AA), is oxidized. There is reasonable homology between soybean enzyme (SLO) and the human one [2]. This homology becomes more identical (50%) within 8Å in the active site pocket. Obviously SLO is much more accessible than the human one. Therefore, one can expect that the results can be extendable to the human LO. In this study, on the basis of recently report on inhibitory potency of eugenol and esteragol compounds [3], a group of 2-allyl-1-alkoxy-4-methoxybenzene were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO). Some compounds showed best IC50s in SLO inhibition. All compounds were docked in SLO active site and the SAR (structure activity relationship) studies suggested that the inhibitory activity of these molecules largely depends on the orientation of allyl group toward the FeIII–OH moiety in the active site of enzyme and also, it is resulted that long and volume lipophilic chain of the alkyl part of the ethers would effect on inhibitory potency variation of the synthetic compounds. So it is assumed that lipophilic interaction of ligand–enzyme would be in charge of inhibiting the enzyme activity.

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