Antibiotic Guanacastane Diterpenoids with Two New Skeletons from Psathyrella candolleana Uncovered by Semisolid and Liquid Media

The culture of Psathyrella candolleana in host Dioscorea opposite medium produced seven new guanacastane diterpenoids, psayamin (1) as an unprecedented 5/7/6/6/6/6/7/5-fused octacyclic spiro scaffold both under liquid and semisolid conditions, psathins A–C (4–6) with a 5/7/6 tricyclic backbone by liquid medium, psathins D–E (7–8) as the same unprecedented skeletons of 5/6/7/6-fused tetracyclic or 6/7/6 tricyclic structures, and psathin F (9) with a 5/7/5/6 tetracyclic backbone by semisolid medium. The structures were elucidated by detailed spectroscopic analyses and those of 1 and 7 were determined by single-crystal X-ray crystallography. The semisolid culture led to four structure types of the guanacastane diterpenoid. Compound 5 showed antifungal activity against phytopathogen Fusarium incarnatum with a minimum inhibitory concentration (MIC) of 8 μg/mL, while compound 4 showed significant antifungal activity against Alternaria sp. with an MIC of 2 μg/mL. Compounds 1 and 8 also showed antifeedant activities against the silkworms with the feeding deterrence indices of 50%, at the concentrations of 50 μg/cm2. Compound 1 showed significant cytotoxicity with IC50 at 10.87 ± 0.24–15.96 ± 0.30 μM and anti-acetylcholinesterase activity with IC50 at 37.3 μM. Also, compound 1 remarkably induced apoptosis of HL-60 at 10, 20 μM in a concentration-dependent manner. The spiral ring of 1 was vital in cytotoxicity and anti-acetylcholinesterase activity. The different media fermented by P. candolleana resulted in the chemical diversity of bioactive guanacastane diterpenoids and potential applications in the agricultural and food functions.