The Khamkhains, Neurotrophic Drimane-Type Sesquiterpenoids Derived from a Polyporaceous Basidiomycete Originating from Thailand

Eight unprecedented terpenoids were isolated from submerged cultures of a polyporoid basidiomycete originating from Thailand (which had been referred to as “Cerrena sp.” in a previous publication) by preparative chromatography. Their chemical structures were elucidated by extensive two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. One of the compounds was crystallized, and its absolute configuration was established by X-ray crystallography. Among the isolated metabolites were several members of the rare nitrogen-containing drimane type and one dimeric drimane, which consists of a nitrogen-containing monomer and a regular monomer. The latter compound represents a hitherto unknown type of terpenoid natural product. The metabolites were subjected to a biological characterization, and some of them showed significant neurotrophic effects. Notably, several of the compounds significantly enhanced the outgrowth of neurites in PC12 cells when treated with 5 ng/mL nerve growth factor. On the other hand, they were devoid of significant cytotoxic and antimicrobial effects.