Hungarian mushrooms as untapped source of natural products: from screening studies to biologically active metabolites

Mushrooms have long been recognized for their therapeutic value, particularly in the traditional medicines of several countries in the Far East. Hungary thanks to its varied relief is one of the European countries with higher biodiversity in wild mushrooms: more than 3000 species are indigenous to Hungary, but to date, however, there has been little rigorous scientific study of these mushrooms in terms of their potential pharmacological benefits. In our research program started in 2012, we aimed to identify fungal species with remarkable antiproliferative, antioxidant and antibacterial activities. More than 40 species were screened for their pharmacological properties; several species demonstrated significant biological activity with moderate to high potential. Species exhibiting outstanding biological activity e.g. Gymnopus fusipes and Tapinella atrotomentosa were selected for further detailed mycochemical and pharmacological analyses. Bioactivity-guided isolation led to the identification of two novel cyclopeptides from G. fusipes. Gymnopeptides A and B are the largest cyclic peptides of mushroom origin: they are constituted of 18 monomers, compared to the well-known cyclic peptides of the poisonous Amanita and Omphalotus species, which have 7 – 12 monomers in their molecules. The antiproliferative property of the isolated compounds was investigated on different human cancer cell lines. Gymnopeptides A and B exhibited outstanding cell growth inhibitory property with IC50 values in nanomolar range. Detailed investigation of T. atrotomentosa, a species with antioxidant and antimicrobial potentials in preliminary studies revealed terphenyl quinone type compounds with notable antioxidant activity in ORAC assay. Our results highlight the importance of further in-depth studies to explore the fairly neglected field of macrofungi.