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 lipoxyg...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2012-08, Vol.20 (16), p.5027-5032
Hauptverfasser:	Wisastra, Rosalina, Ghizzoni, Massimo, Boltjes, André, Haisma, Hidde J., Dekker, Frank J.
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric properties Anacardic acid Anacardic Acids - chemistry Arachidonate 5-lipoxygenase Arachidonate 5-Lipoxygenase - metabolism binding sites Biological and medical sciences Dose-Response Relationship, Drug Enzyme activation Enzyme Activation - drug effects Enzyme inhibition Fatty acids Food industries Fruit and vegetable industries Fundamental and applied biological sciences. Psychology Glycine max - enzymology Inflammation Inflammatory diseases inhibitory concentration 50 Linoleic acid Lipoxygenase Lipoxygenase - metabolism Lipoxygenase Inhibitors - chemical synthesis Lipoxygenase Inhibitors - chemistry Lipoxygenase Inhibitors - pharmacology Medical sciences Molecular Structure natural products Oxidation Pharmacology. Drug treatments Potato 5-LOX potatoes salicylates Salicylates - chemical synthesis Salicylates - chemistry Salicylates - pharmacology Salicylic acid screening Solanum tuberosum Solanum tuberosum - enzymology Soybean lipoxygenase-1 Soybeans Structure-Activity Relationship
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Zusammenfassung:	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 IC50 of 52μM, 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.
ISSN:	0968-0896 1464-3391
DOI:	10.1016/j.bmc.2012.06.019