Calmodulin Inhibitors from Aspergillus stromatoides

From the organic extract of the culture media of Aspergillus stromatoides, emodin (1), ω-hydroxyemodin (2), citrinin (3), methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), and coniochaetone A (5) were isolated. All the compounds were tested for their abilities to quench the fluorescence of the calmodulin (CaM) biosensor hCaM M124C-mBBr. Only anthraquinones 1 and 2 quenched the fluorescence of this biosensor in a concentration-dependent manner with K _d values of 0.33 and 0.76µM, respectively. The results were compared with those of chlorpromazine (CPZ), a classical inhibitor of CaM, with a K _d value of 1.25µM. Docking analysis revealed that 1 and 2 bind to the same pocket of CPZ. The CaM inhibitor properties of 1 and 2 were correlated with some of their reported biological activities. The X-ray structure of 5 is described for the first time.