Ilyomycins A - K, radicicol-type resorcylic acid lactones as potential immunosuppressants from a soil-derived Ilyonectria sp.

Eleven previously undescribed radicicol-type resorcylic acid lactones (RALs), namely ilyomycins A - K (1-9, 10a and 10b), were isolated and identified from the fermented rice culture of a soil-derived fungus, Ilyonectria sp. (strain sb65). Their gross structures were determined by extensive spectroscopic data, and the absolute configurations were elucidated by single-crystal X-ray diffraction, the modified Mosher's method, and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiment. Among them, 10a and 10b were a pair of inseparable regioisomers via intramolecular transacetylation. Compounds 3, 7, 8 and 10a/10b displayed immunosuppressive activities against T cell proliferation with IC50 values ranging from 1.2 to 21.7 µM, and against B cell proliferation with IC50 values ranging from 1.1 to 20.1 µM, which suggested that the α, ß-unsaturated ketone from C-8 to C-10 was an important pharmacophore. Further study revealed that ilyomycin C (3) exerted anti-proliferative effect on T lymphocytes through Hsp90 inhibition.

Harzianic acids and oxazolidinone from the endophytic fungus Ilyonectria sp. and their cytotoxicity activity.

Four undescribed compounds including three harzianic acids (1, 3 and 4) and one oxazolidinone (2), along with three known ones (5-7) were isolated from the solid fermented product of endophytic fungus Ilyonectria sp., their structures were elucidated as 1-amino-harzianic acid (1), ilyonectria-oxazolidinone (2),10'-nor- isoharzianic acid (3), isohomoharzianic acid (4), harzianic acid (5), isoharzianic acid (6), homoharzianic acid (7) by means of detailed chemical evidences and spectroscopic data analysis. All the compounds were evaluated for cytotoxicity against SMMC-7721 human cancer cell lines by MTS assay. Among the seven tested compounds, 1-amino-harzianic acid (1) demonstrated well cytotoxic activity against SMMC-7721 with IC50 value of 26.84 µM. The results of molecular docking indicated that compound exhibited moderate anti-tumor activity may through binding to apoptosis related proteins.