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 B2 (TXB2) and superoxide anion (O2-) 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 μM) with low lactate dehydrogenase release and minimal mitochondrial dehydrogenase inhibition. While a lack of O2- 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.