title: Bisabolane Sesquiterpenoids from the Plant Endophytic Fungus Paraconiothyrium brasiliense.
abstract: 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.
authors.affiliation: †State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: ‡Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: †State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Liangdong
authors.initials: L
authors.lastname: Guo
authors.affiliation: ‡Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Che
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D006593:Hexokinase