Cotylenin F

Five new diterpenoid glycosides, dongtingnoids A-E (1-5), two new diterpenoid aglycones, dongtingnoids F and G (6 and 7), and two known analogues, cotylenins E and J (8 and 9), belonging to the fusicoccane family, were isolated from the fungus Penicillium sp. DT10, which was derived from wetland soil from Dongting Lake. Their structures and absolute configurations were elucidated based on spectroscopic analyses, acid hydrolysis, ECD calculations, and X-ray crystallography. Dongtingnoid C (3) is the first 16-nor-fusicoccane diterpenoid glycoside reported and is proposed to form by oxidative demethylation. Compounds 1, 4, and 5 showed comparable seed-germination-promoting activities to that previously reported for the growth regulator cotylenin E (8).

To find new metabolites similar to cotylenins and fusicoccins from the fungus Alternaria brassicicola, screening tests were carried out using the lettuce seed dormancy breaking assay. Activity-guided fractionation of the EtOAc extract from the culture using the assay afforded the isolation of two novel fusicoccane diterpenoids named brassicicenes J (1) and K (2), along with three known brassicicenes A (3), B (4), and F (5). Their structures were elucidated from extensive NMR spectral data and by comparison of these with those reported in the literature. Brassicicenes (1-5) exhibited weak to moderate seed dormancy breaking activities against lettuce seeds in the presence of abscisic acid. In addition, the necrotic/apoptotic activities of the brassicicenes (1-5), fusicoccin A (6) and cotylenin A (7) were evaluated by determining their cytotoxicity, cell viability and caspase-3/7 activation on the HL-60 cell line. Brassicicene K (2) exhibited similar cytostatic profiles to that of cotylenin A (7), and brassicicenes J (1), A (3), B (4), and F (5) exhibited necrotic activity. This is the first report of the seed dormancy breaking activity of brassicicenes in plants, and of necrotic/apoptotic activity in mammalian cells.