Immunomodulatory N-acyl Dopamine Glycosides from the Icelandic Marine Sponge Myxilla incrustans Collected at a Hydrothermal Vent Site

Abstract

A chemical investigation of the sponge (Porifera) Myxilla incrustans collected from the unique submarine hydrothermal vent site Strytan, North of Iceland, revealed a novel family of closely related N-acyl dopamine glycosides. Three new compounds, myxillin A (1), B (2) and C (3), were isolated and structurally elucidated using several analytical techniques, such as HR-MS, 1D and 2D NMR spectroscopy. Myxillin A (1) and B (2)were shown to be structurally similar, composed of a dopamine moiety, but differ in the acyl chain length and saturation. The myxillin C (3) has a dehydrotyrosine moiety composing the same acyl chain and glycosylation as myxillin B (2). Myxillins A (1) and C (3) were tested for immunomodulating activity in an in vitro dendritic cell model. Dendritic cells matured and stimulated in the presence of myxillin A (1) secreted lower levels of IL-12p40, whilst dendritic cells matured and stimulated in the presence of myxillin C (3) secreted lower levels of IL-10 compared with dendritic cells matured and stimulated in the presence of the solvent alone. These opposing results indicate that the structural differences in the aromatic ring part of the molecules could have an impact on the immunological effects of dendritic cells. These molecules could, therefore, prove to be important in preventing inflammatory diseases on the one hand, and inducing a response to fight tumors and/or pathogens on the other hand. Further studies will be needed to confirm these potential uses.

Marine natural products

“…A number of new glyceride (788 and 789) and ceramide (790-793) lipids have been reported from species of Theonella and Erylus, 394,395 while branched fatty acids (794 and 795), polyoxygenated fatty acid amides (796 and 797) and N-acyldopamine glycosides 798-801 were sourced from Asteropus, Melonanchora, Myxilla and Theonella sponges. [396][397][398][399] Unusually, only one new polyacetylene 802 was reported in 2016, from Halichondria panicea. 400 Examination of the two-sponge association between Xestospongia deweerdtae and Plakortis halichondrioides, in addition to P. zyggompha, resulted in the isolation of 6-epi-7,8dihydroplakortide K 803, plakortide AA 804, and three chemically unstable plakinic acids N-P 805-807.…”

Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters

“…The diversity of biogenic amines in animals has been produced by several evolutionarily conserved enzymes (figure 4). Ctenophores [185], sponges [66,[186][187][188][189][190][191], placozoans and cnidarians [192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209][210] might synthesize additional catecholamines and indolamines, but their locations and potential transmitter functions should be subject to careful investigations. There are several, mostly early, reports for the presence of serotonin, dopamine and noradrenaline in cnidarians [197,200,[211][212][213][214][215][216][217][218][219][220], but it was not consistent with genomic data about predicted synthetic enzymes [176,177,179].…”

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFNγ-stimulated endothelial cells

“…We and others have previously reported that N-acyl dopamine derivatives (NADD) harbour biological properties that might be useful for preventing transplantation associated injury 29–31 . As such they limit cold inflicted 32 and ischemia reperfusion-injury 33 and modulate inflammation through inhibition of NFκB 21,34 . We also have reported that NOD, a short synthetic NADD, transiently inhibits T-cell activation and demonstrates synergy with CNI in suppressing T-cell activation 22 .…”