Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases.
Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxygenase-1 (SLO-1) inhibitor and a potato 5-lipoxygenase (5-LOX) activator from a screening of a focused compound collection around the natural product anacardic acid. The natural product anacardic acid inhibits SLO-1 with an IC(50) of 52 μM, whereas the inhibitory potency of the novel mixed type inhibitor 23 is fivefold enhanced. In addition, another derivative (21) caused non-essential activation of potato 5-LOX. This suggests the presence of an allosteric binding site that regulates the lipoxygenase activity.
Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Rosalina
R
Wisastra
Massimo
M
Ghizzoni
André
A
Boltjes
Hidde J
HJ
Haisma
Frank J
FJ
Dekker
D048729:Anacardic Acids / Q000737:chemistry*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011198:Solanum tuberosum / Q000201:enzymology; D013025:Glycine max / Q000201:enzymology; D013329:Structure-Activity Relationship
D048729:Anacardic Acids; D016859:Lipoxygenase Inhibitors; D012459:Salicylates; C088115:anacardic acid; D008084:Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase