具有5-LOX抑制活性的丁香酚衍生物的研究。

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
José L Pereira Filho, Renato B Pereira, Tatiana F Vieira, Sérgio F Sousa, José R A Coelho, Nuno F S Pinto, Catarina M M Coelho, Maria José G Fernandes, Elisabete M S Castanheira, Maria S T Gonçalves, David M Pereira
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引用次数: 0

摘要

丁香酚(4-烯丙基-2-甲氧基酚)是许多植物精油中的主要化学成分。该分子的一些生物学特性已经被描述,包括与炎症反应相关的酶靶标的调节,如5-脂氧合酶(5-LOX)。因此,人们有兴趣扩大这种分子的化学空间,以开发用于炎症条件的新分子。我们描述了几种丁香酚衍生物的化学计量分析,结果表明母体分子的化学空间被成功地扩展了。所有分子都被评估对5-LOX的抑制作用,5-LOX是炎症途径的重要参与者。4个衍生物均表现出明显的5-LOX抑制活性,有待进一步研究。最有希望的化合物是4-烯丙基苯-1,2-二醇2、乙基-4-(4-烯丙基-2-甲氧基苯氧基)丁酸酯4e、3-(2-甲氧基-2-甲基)苯氧基)乙酸丙酯5d和4-(3-(叔丁基)-2-羟丙基)-2-甲氧基苯酚7c,它们对5-LOX具有亲和力和稳定性,这有助于阐明这些分子相互作用和抑制该酶的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Development of eugenol derivatives with 5-LOX inhibitory activity.

Eugenol (4-allyl-2-methoxyphenol), is the major chemical constituent in the essential oil of numerous plant species. Several biological properties have been described for this molecule, including modulation of enzymatic targets relevant for the inflammatory response, such as 5-lipoxygenase (5-LOX). As so, there is interest in expanding the chemical space of this molecule to develop new molecules to be used in inflammatory conditions. We describe the chemometric analysis of several eugenol derivatives, which show that the chemical space of the parent molecule was successfully expanded. All molecules were evaluated for their inhibition towards 5-LOX, an important player in inflammatory pathways. Four derivatives exhibited significant 5-LOX inhibitory activity, which prompted further studies. The most promising compounds, 4-allylbenzene-1,2-diol 2, ethyl-4-(4-allyl-2-methoxyphenoxy)butanoate 4e, 3-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)propyl acetate 5d and 4-(3-(tert-butoxy)-2-hydroxypropyl)-2-methoxyphenol 7c, were submitted to in silico assays to validate their affinity and stability towards 5-LOX, which helped clarify the mechanism by which these molecules interact and inhibit this enzyme.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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