Fungal Metabolites as Potent Protein Kinase Inhibitors: Identification of a Novel Metabolite and Novel Activities of Known Metabolites

Abstract

A novel undecylresorcinol dimer (1) was isolated from Coleophoma sp. and inhibited cFMS receptor tyrosine kinase (IC50 of 0.4 μM), with greater than 10-fold selectivity versus nine other protein kinases. The known fungal metabolites balanol and altenusin inhibited cFMS kinase and pp60c-Src kinase, respectively, even more potently and selectively. Altenusin inhibited pp60c-Src with an IC50 of 20 nM and a selectivity of at least 400-fold versus nine other protein kinases. Balanol inhibited cFMS receptor kinase with an IC50 of 1 nM and selectivities of 14-75-fold versus pp60c-Src and VEGF receptor kinases and greater than 10,000-fold versus seven other kinases. Keywords: fungal metabolite, protein kinase inhibitor, cfms receptor tyrosine kinase, pp60c-src kinase, balanol, altenusin, alternariol