Oxylipins from the microalgae Chlamydomonas debaryana and Nannochloropsis gaditana and their activity as TNF-α inhibitors

The chemical study of the microalgae Chlamydomonas debaryana and Nannochloropsis gaditana has led to the isolation of oxylipins. The samples of C debaryana have yielded the compounds (4Z,7Z,9E,11S,13Z)-11-hydroxyhexadeca-4,7,9,13-tetraenoic acid (1), (4Z,7E,9E,13Z)-11-hydroxyhexadeca-4,7,9,13-tetraenoic acid (2), (4Z,6E,10Z,13Z)-8-hydroxyhexadeca-4,6,10,13-tetraenoic acid (3), (4Z,8E,10Z,13Z)-7-hydroxyhexadeca-4,8,10,13-tetraenoic acid (4), and (5E,7Z,10Z,13Z)-4-hydroxyhexadeca-5,7,10,13-tetraenoic acid (5), which are derived from the fatty acid 16:4 Delta(4,7,10,13) together with the compound (5Z,9Z,11E,15Z)-13-hydroxyoctadeca-5,9,11,15-tetraenoic acid (7) derived from coniferonic acid (18:4 Delta(5,9,12,15)). In addition, the known polyunsaturated hydroxy acids 11-HHT (6), (5Z,9Z,11E)-13-hydroxyoctadeca-5,9,11-trienoic acid (8), (13S)-HOTE (9), (9E,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (10), 9-HOTE (11), 12-HOTE (12), 16-HOTE (13) and (13S)-HODE (14) have also been obtained. The chemical study of N. gaditana has led to the isolation of the hydroxy acid (15S)-HEPE (15) derived from EPA (20:5 Delta(5,8,11,14,17)). The structures of the isolated compounds were established by spectroscopic means. The optical activity displayed by oxylipins 1, 2, 6, 7, 9, 10, 14, and 15 suggests the occurrence of LOX-mediated pathways in C debaryana and N. gaditana. In anti-inflammatory assays, all the tested compounds inhibited the TNF-alpha production in LPS-stimulated THP-1 macrophages. The most active oxylipin was the C-16 hydroxy acid 1, which at 25 mu M caused a 60% decrease of the TNF-alpha level. (C) 2014 Elsevier Ltd. All rights reserved.