Suppression of leukotriene B4 and tumour necrosis factor alpha release in acute inflammatory responses by novel prenylated hydroquinone derivatives.
A series of prenyl hydroquinone derivatives synthesized as structural analogs of marine products were tested for their effects on inflammatory responses in vitro and in vivo. 2-Prenyl-1,4-hydroquinone (H1), 2-diprenyl-1,4-hydroquinone (H2), 2-triprenyl-1,4-hydroquinone (H3) and 2-tetraprenyl-1,4-hydroquinone (H4) scavenged reactive oxygen species and inhibited 5-lipoxygenase (5-LO) activity in human neutrophils. The inhibition of 5-LO activity was demonstrated in vivo in the mouse air pouch injected with zymosan and arachidonic acid-induced ear inflammation. The four compounds suppressed the production of tumour necrosis factor alpha (TNFalpha) in J774 cells stimulated with lipopolysaccharide (LPS) and also in vivo in the mouse air pouch injected with zymosan. In addition, all prenyl-hydroquinones inhibited the release of nitrite and PGE2 in LPS-stimulated J774 cells, without direct effects on cyclo-oxygenase-1 (COX-1), cyclo-oxygenase-2 (COX-2) or inducible nitric oxide synthase (iNOS) activities in several cell-free systems. The reduction in the length of the lateral chain in prenyl-hydroquinones (1-4 isoprene units) with respect to their marine analogs (7-8 isoprene units) has improved the anti-inflammatory activity of this class of compounds. Marine natural products may be a model to design new anti-inflammatory agents.
Terencio
M C
MC
Department of Pharmacology, University of Valencia, Faculty of Pharmacy, Burjassot, Spain.
Ferrándiz
M L
ML
Posadas
I
I
Roig
E
E
de Rosa
S
S
De Giulio
A
A
Payá
M
M
Alcaraz
M J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000633:toxicity; D002478:Cells, Cultured; D003864:Depression, Chemical; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced; D006801:Humans; D006873:Hydroquinones / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D009573:Nitrites / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D006873:Hydroquinones; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015232:Dinoprostone