Clicked Cinnamic/Caffeic Esters and Amides as Radical Scavengers and 5-Lipoxygenase Inhibitors

International Journal of Medicinal Chemistry. 2014;2014 DOI 10.1155/2014/931756

 

Journal Homepage

Journal Title: International Journal of Medicinal Chemistry

ISSN: 2090-2069 (Print); 2090-2077 (Online)

Publisher: Hindawi Limited

LCC Subject Category: Medicine: Therapeutics. Pharmacology

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML

 

AUTHORS

Jérémie A. Doiron (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Benoît Métayer (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Ryan R. Richard (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Dany Desjardins (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Luc H. Boudreau (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Natalie A. Levesque (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Jacques Jean-François (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Samuel J. Poirier (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Marc E. Surette (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)
Mohamed Touaibia (Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, E1A 3E9, Canada)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 18 weeks

 

Abstract | Full Text

5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a–h and amides 9a–h as well as caffeic esters 15a–h and amides 16a–h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10–20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.