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Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors.


ABSTRACT: 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??M). 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.

SUBMITTER: Doiron JA 

PROVIDER: S-EPMC4207410 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors.

Doiron Jérémie A JA   Métayer Benoît B   Richard Ryan R RR   Desjardins Dany D   Boudreau Luc H LH   Levesque Natalie A NA   Jean-François Jacques J   Poirier Samuel J SJ   Surette Marc E ME   Touaibia Mohamed M  

International journal of medicinal chemistry 20140218


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)-catalyz  ...[more]

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