PAECILOQUINONE-A, PAECILOQUINONE-B, PAECILOQUINONE-C, PAECILOQUINONE-D, PAECILOQUINONE-E AND PAECILOQUINONE-F - NEW POTENT INHIBITORS OF PROTEIN-TYROSINE KINASES PRODUCED BY PAECILOMYCES-CARNEUS .1. TAXONOMY, FERMENTATION, ISOLATION AND BIOLOGICAL-ACTIVITY

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 0.4 mu M. Dependent on the fermentation conditions, partially different sets of paeciloquinones may be produced. An HPLC method allows separation of all major active components.