Potential antihyperlipidemic polyketones from endophytic Diaporthe sp. JC-J7 in Dendrobium nobile.

ABSTRACT

Eleven new polyketones named diaporthsins A-K (1-11) were isolated from the fermentation of Diaporthe sp. JC-J7. The chemical structures of compounds (1-11) were elucidated by spectroscopic methods including HRESIMS, 2DNMR, NMR and chemical methods. Compound 11 features an unusual acyclic polyketone-phenolic polyketone hybrid structure that integrates the characteristics of different fungal metabolites (cytosporone and multiplolide). Compound 3 was the only C12-polyketone obtained in this research. These new polyketones showed inhibitory activity on triglycerides (TG) in steatosis hepatocyte L-02 cells. Among them, compound 5 and (4E)-6,7,9-trihydroxydec-4-enoic acid displayed inhibitory activities on TG in steatotic L-02 cells with inhibition ratios of 26% and 21% at concentration of 5 µg mL-1; also, inhibition ratios of 8-O-acetylmultiplolide A and phomopsisporone A at concentration of 5 µg mL-1 were calculated to be about 24% and 16%, respectively, which were equivalent to the antihyperlipidemic activity of lovastatin. The preliminary structure-activity relationship indicated that acetyl at C-8 can increase the antihyperlipidemic activity of multiplolide A and the glycol ester and hydroxyl at C-6 can also increase the corresponding activity of diaporthsin B.