Bioactive secondary metabolites from an Endolichenic Fungus, Corynespora sp. inhabiting the Cavern beard Lichen, Usnea cavernosa

Abstract

Bioactive secondary metabolites of an endolichenic fungal strain, Corynespora sp., occurring in the beard cavern lichen Usnea cavernosa (cavern beard lichen; Parmeliaceae; Lecanorales), was investigated. Although a number of lichens, their fungal mycobionts, and a lichenicolous fungus from different geographic locations have been subjected to chemical investigations, leading to the isolation and characterization of a variety of metabolites, to the best our knowledge this constitutes the first report of secondary metabolites from an endolichenic fungus. An EtOAc extract of Corynespora sp. cultured in potato dextrose broth (PDB) exhibited significant cell migration inhibitory activity in a wound-healing assay (WHA) using the metastatic prostate cancer cell line, PC-3M, at a noncytotoxic concentration of 5 µg/mL. We report the bioassay-guided isolation of two new heptaketides, corynesporol (1) and 1-hydroxydehydroherbarin (2), together with herbarin (3) and the chemical transformation of 1-3 yielding compounds, dehydroherbarin (4) and four new acetylated derivatives of the heptadetides. The structures of 1–4 and the acetylated derivatives were elucidated by spectroscopic methods and all compounds were evaluated for their cytotoxicity and ability to inhibit migration of human metastatic breast and prostate cancer cell lines MDA-MB-231 and PC-3M, respectively. Dehydroherbarin (4) inhibited migration of both cell lines at concentrations not toxic to these cell lines.