title: Cimicifoetones A and B, Dimeric Prenylindole Alkaloids as Black Pigments of Cimicifuga foetida.
abstract: Two dimeric prenylindole alkaloids with a unique indole-benzoindolequinone skeleton, cimicifoetones A (1) and B (2), were isolated as black pigments from the rhizomes of Cimicifuga foetida. The structures were elucidated by spectroscopic methods including HRMS and 2D NMR, as well as single-crystal X-ray diffraction and computational chemical modeling techniques. Cimicifoetones A and B represented the first examples of dimeric indole alkaloids generated through [4+2] Diels-Alder cycloaddition between the prenyl side chain in one 3-prenylindole and the aromatic ring in another. The two compounds showed promising anti-proliferative activity on seven tumor cell lines with IC50values in the range of 1.36-21.09 μm. Flow cytometric and western blot analysis revealed that compound 2 induced cell apoptosis via death receptor-mediated extrinsic and mitochondrial-mediated intrinsic pathways.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Yu-E
authors.initials: YE
authors.lastname: Yu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Sheng
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Jian-Xia
authors.initials: JX
authors.lastname: Mo
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1# Keyuan 4th Road, High-tech Zone, Chengdu, 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.
authors.forename: Li-She
authors.initials: LS
authors.lastname: Gan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D031885:Cimicifuga / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; C000626307:cimicifoetone A; C000626308:cimicifoetone B
keywords: alkaloids; apoptosis; cimicifoetones; cytotoxicity; natural products; structure elucidation