Marine sponge Hymeniacidon sp amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation

The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi-synthetic analogs (6 and 7) on thromboxane B-2 (TXB2) and superoxide anion (O-2(-)) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB2 (IC50 = 0.20-4.69 mu M) with low lactate dehydrogenase release and minimal mitochondrial dehydrogenase inhibition. While a lack of O-2(-) inhibition would suggest that Hymeniacidon sp. metabolites and derivatives inhibit TXB2 synthesis by a cyclooxygenase-dependent mechanism, their pharmacologic potency and limited in vitro cytotoxicity warrants further investigation to develop them as lead compounds to modulate enhanced TBX2 release by activated microglia in neuroinflammatory disorders. (C) 2011 Elsevier Ltd. All rights reserved.