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Bisabolane Sesquiterpenoids from the Plant Endophytic Fungus Paraconiothyrium brasiliense

Liu, Ling, Chen, Xiaoyan, Li, Dong, Zhang, Yang, Li, Li, Guo, Liangdong, Cao, Ya, Che, Yongsheng
Journal of natural products 2015 v.78 no.4 pp. 746-753
adenosine triphosphate, anticarcinogenic activity, breasts, circular dichroism spectroscopy, enantiomers, endophytes, energy, fermentation, fungi, glucose, hexokinase, high performance liquid chromatography, inhibitory concentration 50, metabolites, neoplasm cells, neoplasms, nuclear magnetic resonance spectroscopy, sesquiterpenoids
Brasilamides E–J (1–6), the bisabolane sesquiterpenoids with the 3-cyclohexylfuran (1 and 2) and 3-cyclohexylfuranone (3–6) skeletons, were isolated from the scale-up fermentation cultures of the plant endophytic fungus Paraconiothynium brasiliense Verkley. Although brasilamide E (1) is a known metabolite, its structure elucidation has yet to be described. The structures of 1–6 were elucidated primarily by NMR experiments. Compounds 3–6 were found to be racemic, and 3 was further separated into enantiomers 3a and 3b on a chiral HPLC column. The absolute configurations of 3a and 3b were assigned by electronic circular dichroism calculations. Compound 1 selectively inhibited the proliferation of the breast (MCF-7) and gastric (MGC) cancer cell lines, with IC₅₀ values of 8.4 and 14.7 μM, respectively. Initial mechanistic investigation revealed that compound 1 inhibited the expression of a key energy metabolic enzyme, hexokinase II (HK2), in MCF-7 cells, which resulted in dysfunction of glucose metabolism and ATP depletion and eventually inhibited the proliferation of the breast cancer cells.