New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition
Leukotrienes are biosynthesized by the conversion of arachidonic acid by 5-Lipoxygenase and play a key role in many inflammatory disorders. Inspired by caffeic acid phenylethyl ester (CAPE) (2) and an analog carrying a triazole substituted by cinnamoyl and 5-LO inhibitors recently reported by our te...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2017/2380531 |
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| author | Pierre-Philipe Roy Diene Faye Sébastien Blanchard Marc Cormier Jérémie A. Doiron Marc E. Surette Mohamed Touaibia |
| author_facet | Pierre-Philipe Roy Diene Faye Sébastien Blanchard Marc Cormier Jérémie A. Doiron Marc E. Surette Mohamed Touaibia |
| author_sort | Pierre-Philipe Roy |
| collection | DOAJ |
| description | Leukotrienes are biosynthesized by the conversion of arachidonic acid by 5-Lipoxygenase and play a key role in many inflammatory disorders. Inspired by caffeic acid phenylethyl ester (CAPE) (2) and an analog carrying a triazole substituted by cinnamoyl and 5-LO inhibitors recently reported by our team, sixteen new CAPE analogs bearing substituted triazole were synthesized by copper catalyzed Huisgen 1,3-dipolar cycloaddition. Compound 10e, an analog bearing p-CF3 phenethyl substituted triazole, was equivalent to CAPE (2) but clearly surpassed Zileuton (2), the only approved 5-LO inhibitor. Substitution of the phenethyl moiety by cyclohexylethyl, as with 12g, clearly increased 5-LO inhibition which confirms the importance of hydrophobic interactions. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds as leukotrienes biosynthesis inhibitors. |
| format | Article |
| id | doaj-art-220cbd36893348cb89aa3efa95892acf |
| institution | OA Journals |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-220cbd36893348cb89aa3efa95892acf2025-08-20T02:04:05ZengWileyJournal of Chemistry2090-90632090-90712017-01-01201710.1155/2017/23805312380531New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase InhibitionPierre-Philipe Roy0Diene Faye1Sébastien Blanchard2Marc Cormier3Jérémie A. Doiron4Marc 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 biosynthesized by the conversion of arachidonic acid by 5-Lipoxygenase and play a key role in many inflammatory disorders. Inspired by caffeic acid phenylethyl ester (CAPE) (2) and an analog carrying a triazole substituted by cinnamoyl and 5-LO inhibitors recently reported by our team, sixteen new CAPE analogs bearing substituted triazole were synthesized by copper catalyzed Huisgen 1,3-dipolar cycloaddition. Compound 10e, an analog bearing p-CF3 phenethyl substituted triazole, was equivalent to CAPE (2) but clearly surpassed Zileuton (2), the only approved 5-LO inhibitor. Substitution of the phenethyl moiety by cyclohexylethyl, as with 12g, clearly increased 5-LO inhibition which confirms the importance of hydrophobic interactions. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds as leukotrienes biosynthesis inhibitors.http://dx.doi.org/10.1155/2017/2380531 |
| spellingShingle | Pierre-Philipe Roy Diene Faye Sébastien Blanchard Marc Cormier Jérémie A. Doiron Marc E. Surette Mohamed Touaibia New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition Journal of Chemistry |
| title | New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition |
| title_full | New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition |
| title_fullStr | New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition |
| title_full_unstemmed | New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition |
| title_short | New Caffeic Acid Phenylethyl Ester Analogs Bearing Substituted Triazole: Synthesis and Structure-Activity Relationship Study towards 5-Lipoxygenase Inhibition |
| title_sort | new caffeic acid phenylethyl ester analogs bearing substituted triazole synthesis and structure activity relationship study towards 5 lipoxygenase inhibition |
| url | http://dx.doi.org/10.1155/2017/2380531 |
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