New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis
Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated thera...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/6904634 |
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| author | Luc H. Boudreau Grégoire Lassalle-Claux Marc Cormier Sébastien Blanchard Marco S. Doucet Marc E. Surette Mohamed Touaibia |
| author_facet | Luc H. Boudreau Grégoire Lassalle-Claux Marc Cormier Sébastien Blanchard Marco S. Doucet Marc E. Surette Mohamed Touaibia |
| author_sort | Luc H. Boudreau |
| collection | DOAJ |
| description | Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues. In this study, we investigated structural analogues of caffeic acid phenethyl ester, a naturally-occurring 5-lipoxygenase inhibitor, in an attempt to enhance the inhibitory activity against 5-lipoxygenase and determine structure-activity relationships. These compounds were investigated for their ability to attenuate the biosynthesis of leukotrienes. Compounds 13 and 19, phenpropyl and diphenylethyl esters, exhibited significantly enhanced inhibitory activity when compared to the reference molecules caffeic acid phenethyl ester and zileuton. |
| format | Article |
| id | doaj-art-547be332a20f4d32bbb7e377daf63e50 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-547be332a20f4d32bbb7e377daf63e502025-08-20T02:05:45ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/69046346904634New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene BiosynthesisLuc H. Boudreau0Grégoire Lassalle-Claux1Marc Cormier2Sébastien Blanchard3Marco S. Doucet4Marc E. Surette5Mohamed Touaibia6Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, E1A 3E9, CanadaLeukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues. In this study, we investigated structural analogues of caffeic acid phenethyl ester, a naturally-occurring 5-lipoxygenase inhibitor, in an attempt to enhance the inhibitory activity against 5-lipoxygenase and determine structure-activity relationships. These compounds were investigated for their ability to attenuate the biosynthesis of leukotrienes. Compounds 13 and 19, phenpropyl and diphenylethyl esters, exhibited significantly enhanced inhibitory activity when compared to the reference molecules caffeic acid phenethyl ester and zileuton.http://dx.doi.org/10.1155/2017/6904634 |
| spellingShingle | Luc H. Boudreau Grégoire Lassalle-Claux Marc Cormier Sébastien Blanchard Marco S. Doucet Marc E. Surette Mohamed Touaibia New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis Mediators of Inflammation |
| title | New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis |
| title_full | New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis |
| title_fullStr | New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis |
| title_full_unstemmed | New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis |
| title_short | New Hydroxycinnamic Acid Esters as Novel 5-Lipoxygenase Inhibitors That Affect Leukotriene Biosynthesis |
| title_sort | new hydroxycinnamic acid esters as novel 5 lipoxygenase inhibitors that affect leukotriene biosynthesis |
| url | http://dx.doi.org/10.1155/2017/6904634 |
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