Sadeghian Hamid, Attaran Neda, Jafari Zeinab, Saberi Mohammad Reza, Seyedi Seyed Mohammad, Eshghi Hossein, Pordel Mehdi, Riazi Mohammad Mahdi
Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad 91389-13131, Iran.
Bioorg Med Chem. 2009 Mar 15;17(6):2327-35. doi: 10.1016/j.bmc.2009.02.009. Epub 2009 Feb 13.
A group of 4-methoxyphenylacetic acid esters were designed, synthesized and evaluated as potential inhibitors of soybean 15-lipoxygenase (SLO) on the basis of eugenol and esteragol structures. Compounds 7d-e showed the best IC(50) in SLO inhibition (IC(50)=3.8 and 1.9 microM, respectively). All compounds were docked in SLO active site and showed that carbonyl group of compounds is oriented toward the Fe(III)-OH moiety in the active site of enzyme and fixed by hydrogen bonding with hydroxyl group. It is assumed that lipophilic interaction of ligand-enzyme would be in charge of inhibiting the enzyme activity. The selectivity of the synthetic esters in inhibiting of 15-HLOb was also compared with 15-HLOa by molecular modeling and multiple alignment techniques.
基于丁香酚和甲基丁香酚的结构，设计、合成并评估了一组4-甲氧基苯乙酸酯作为大豆15-脂氧合酶（SLO）的潜在抑制剂。化合物7d - e在抑制SLO方面表现出最佳的半数抑制浓度（IC(50)）（分别为IC(50)=3.8和1.9微摩尔）。所有化合物均对接至SLO活性位点，结果表明化合物的羰基朝向酶活性位点中的Fe(III)-OH部分，并通过与羟基形成氢键而固定。据推测，配体 - 酶之间的亲脂性相互作用负责抑制酶的活性。还通过分子建模和多重比对技术比较了合成酯对15-HLOb和15-HLOa抑制作用的选择性。
