Phenolic Hydrazones are Potent Inhibitors of Macrophage Migration Inhibitory Factor Proinflammatory Activity and Survival Improving Agents in Sepsis

摘要

A series of phenolic hydrazones were synthesized and evaluated for their inhibition of MIF tautomerase activity. Compound >7 emerged as a potent inhibitor of MIF with an IC50 of 130 nM. Compound >7 dose dependently suppressed TNFα secretion from lipopolysaccharide stimulated macrophages. The therapeutic importance of the MIF inhibition by compound >7 is demonstrated by the significant protection from the lethality of sepsis when administration of the compound was initiated in a clinically relevant time frame.