Inhibition of neutrophil elastase and thrombin activity by caffeic acid esters.
Natural and synthetic caffeic acid esters were assayed for their enzymatic activity versus neutrophil elastase (EC 3.4.21.37) and thrombin (EC 3.4.21.5). Lipophilic caffeic acid esters inhibited neutrophil elastase activity and the inhibition rate was enhanced with increasing length of the aliphatic chain of the alcohol component. The geometry of the chain seems to be more important than the number of carbon atoms. The most inhibitory compound was n-octylcaffeic acid ester with an IC50 value of 1.0 microM. Thrombin activity was only weakly inhibited by the caffeic acid esters thus demonstrating a specificity for neutrophil elastase. Because of its critical role in inflammatory processes, inhibition of neutrophil elastase by caffeic acid esters might be of importance in the treatment of inflammation.
Melzig
M F
MF
Institute of Pharmacy, Free University Berlin, Königin-Luise-Str. 2 + 4, D-14195 Berlin, Germany. melzig@zedat.fu-berlin.de
Tran
G D
GD
Henke
K
K
Selassie
C D
CD
Verma
R P
RP
D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors*
D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D019272:Leukocyte Elastase; D013917:Thrombin; C040048:caffeic acid