Cimicifoetones A and B,Dimeric Prenylindole Alkaloids as Black Pigments of Cimicifuga foetida

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 IC₅₀ values 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.