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
{"title":"具有5-LOX抑制活性的丁香酚衍生物的研究。","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","doi":"10.1080/14756366.2025.2535586","DOIUrl":null,"url":null,"abstract":"<p><p>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 <b>2</b>, ethyl-4-(4-allyl-2-methoxyphenoxy)butanoate <b>4e</b>, 3-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)propyl acetate <b>5d</b> and 4-(3-(<i>tert</i>-butoxy)-2-hydroxypropyl)-2-methoxyphenol <b>7c</b>, were submitted to <i>in silico</i> assays to validate their affinity and stability towards 5-LOX, which helped clarify the mechanism by which these molecules interact and inhibit this enzyme.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2535586"},"PeriodicalIF":5.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377105/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of eugenol derivatives with 5-LOX inhibitory activity.\",\"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\",\"doi\":\"10.1080/14756366.2025.2535586\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <b>2</b>, ethyl-4-(4-allyl-2-methoxyphenoxy)butanoate <b>4e</b>, 3-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)propyl acetate <b>5d</b> and 4-(3-(<i>tert</i>-butoxy)-2-hydroxypropyl)-2-methoxyphenol <b>7c</b>, were submitted to <i>in silico</i> assays to validate their affinity and stability towards 5-LOX, which helped clarify the mechanism by which these molecules interact and inhibit this enzyme.</p>\",\"PeriodicalId\":15769,\"journal\":{\"name\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"volume\":\"40 1\",\"pages\":\"2535586\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377105/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14756366.2025.2535586\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Enzyme Inhibition and Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14756366.2025.2535586","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.