Cytotoxic metabolites from the fungal endophyte Alternaria sp and their subsequent detection in its host plant Polygonum senegalense

From the Egyptian medicinal plant Polygonum senegalense the fungal endophyte Alternaria sp. was isolated. Extracts of the fungus grown either in liquid culture or on solid rice media exhibited cytotoxic activity when tested in vitro against L5178Y cells. Chromatographic separation of the extracts yielded 15 natural products, out of which seven were new compounds, with both fungal extracts differing considerably with regard to their secondary metabolites. Compounds 1, 2, 3, 6, and 7 showed cytotoxic activity with EC(50) values ranging from 1.7 to 7.8 mu g/mL. When analyzed in vitro for their inhibitory potential against 24 different protein kinases, compounds 1-3, 5-8, and 15 inhibited several of these enzymes (IC(50) values 0.22-9.8 mu g/mL). Interestingly, compounds 1, 3, and 6 were also identified as constituents of an extract derived from healthy leaves of the host plant P. senegalense, thereby indicating that the production of natural products by the endophyte proceeds also under in situ conditions within the plant host.