TMC-256A1 and C1, New Inhibitors of IL-4 Signal Transduction Produced by Aspergillus niger var niger TC 1629

Abstract

New inhibitors of IL-4 signal transduction, designated as TMC-256A1 and C1, were discovered together with TMC-256B1, a previously known dihydronaphthopyrone, from the fermentation broth of Aspergillus niger var niger TC 1629 by using an IL-4 driven reporter gene assay. Based on spectroscopic analyses, TMC-256A1 and C1 were found to be new members of the naphthopyrone antibiotics. TMC-256A1, B1 and C1 inhibited the IL-4 driven luciferase activity with IC₅₀ values of 25μM, 30μM and 1.7μM, respectively in this assay system. Furthermore, these compounds inhibited the expression of germline Cε mRNA with IC₅₀ values of 6.6μM, 34μM and 0.31μM, respectively.