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

ABSTRACT: The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi-synthetic analogs (6 and 7) on thromboxane B(2) (TXB(2)) and superoxide anion (O(2)(-)) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB(2) (IC(50)=0.20-4.69?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 TXB(2) 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 TBX(2) release by activated microglia in neuroinflammatory disorders.

SUBMITTER: Mayer AM

PROVIDER: S-EPMC3272584 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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

Mayer Alejandro M S AM Avilés Edward E Rodríguez Abimael D AD

Bioorganic & medicinal chemistry 20111109 1

The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi-synthetic analogs (6 and 7) on thromboxane B(2) (TXB(2)) and superoxide anion (O(2)(-)) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB(2) (IC(50)=0.20-4.69μM) with low lactate dehydrogenase release and minimal mitochondrial dehydrogenase inhibition. While a lack of O(2)(-) inhibition would suggest that Hymeniac ...[more]

PMID: 22153874

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