Oxacyclododecindione, a Novel Inhibitor of IL-4 Signaling from Exserohilum rostratum

In a screening program for new metabolites from fungi inhibiting the IL-4 mediated signal transduction, a novel chlorinated macrocyclic lactone, designated as oxacyclododecindione, was isolated from fermentations of the imperfect fungus Exserohilum rostratum. The structure was determined by a combination of spectroscopic techniques. Oxacyclododecindione inhibits the IL-4 induced expression of the reporter gene secreted alkaline phosphatase (SEAP) in transiently transfected HepG2 cells with IC50 values of 20-25 ng/ml (54-67.5 nM). Studies on the mode of action of the compound revealed that the inhibition of the IL-4 dependent signaling pathway is caused by blocking the binding of the activat…