Asterriquinones produced by Aspergillus candinus inhibit binding of the Grb-2 adapter to phosphorylated EGF receptor tyrosine kinase

Five new asterriquinone analogs (2 similar to 4, 6, 7), together with previ ously identified neoasterriquinone (1) and isoasterriquinone (5), were isol ated from a fermentation broth of the fungus Aspergillus candidus and purif ied by HSCCC (high speed counter current chromatography) followed by HPLC. The structures were determined by ID and 2D NMR and MS/MS techniques. All s even showed inhibitory activity against the binding of a recombinant protei n containing the SH2 protein domain of Grb-2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase. Some of these asterriquinones ex hibited specific inhibition of Grb-2 binding compared to Grb-7 and PLC-gamm a.