Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium
- Potent Inhibitors of Pro-Inflammatory Cytokine Production Produced by a Marine-Derived Bacterium
- Wendy K. Strangman; 권학철; David Broide; Paul R. Jensen; William Fenical
- Marine Actinomycetes; asthma; Novel Compounds; inflammation
- Issue Date
- Journal of medicinal chemistry
- VOL 52, NO 8, 2317-2327
- Cytokines produced through the antigen presenting cell (APC)-T-cell interaction play a key role in the
activation of the allergic asthmatic response. Evaluating small molecules that inhibit the production of these
pro-inflammatory proteins is therefore important for the discovery of novel chemical structures with potential
antiasthma activity. We adapted a mouse splenocyte cytokine assay to screen a library of 2,500 marine
microbial extracts for their ability to inhibit TH2 cytokine release and identified potent activity in a marinederived
strain CNQ431, identified as a Streptomyces species. Bioactivity guided fractionation of the organic
extract of this strain led to the isolation of ten new 9-membered bis-lactones, splenocins A-J (1-10). The
new compounds display potent biological activities, comparable to that of the corticosteroid dexamethasone,
with IC50 values from 2 to 50 nM in the splenocyte cytokine assay. This study provides the foundation for
the optimization of these potent anti-inflammatory compounds for development in the treatment of asthma.
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