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)....

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
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Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2025.2535586
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Summary: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.
ISSN:1475-6366
1475-6374