Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor

NF-κB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-κB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (−)-DHMEQ was more potent than its enantiomer. (−)-DHMEQ was found to inhibit NF-κB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells.