Paeciloquinones A, B, C, D, E and F: New Potent Inhibitors of Protein Tyrosine Kinases Produced by Paecilomyces carneus

I. Taxonomy, Fermentation, Isolation and Biological Activity

Abstract

Paeciloquinones A to F as well as versiconol have been isolated as inhibitors of protein tyrosine kinase from the culture broth of the fungus Paecilomyces carneus P-177. The novel anthraquinones inhibit epidermal growth factor receptor protein tyrosine kinase in the micromolar range. Two compounds, paeciloquinones A and C, are potent and selective inhibitors of the v-abl protein tyrosine kinase with an IC₅₀ of 0.4μM. Dependent on the fermentation conditions, partially different sets of paeciloquinones may be produced. An HPLC method allows separation of all major active components.