biostudies-literatureWisastra RNIGMS NIH HHS7763-78https://www.ebi.ac.uk/biostudies/studies/S-EPMC4017091biostudies-literatureUnknown21(24)Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linBioorganic & medicinal chemistryDiscovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.PMC4017091R01 GM097082 -01R01 GM097082Camacho CJKok PAHaisma HJEleftheriadis NBaumgartner MPWisastra RDekker FJfalseDiscovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the lin2013-01-01T00:00:00Z2013 Dec2026-05-02T00:10:10.613Z2019-03-27T01:27:58ZS-EPMC40170912423165010.1016/j.bmc.2013.10.015