Phytochemistry of Clusiaceae benzophenones: Novel bioactive compounds from Garcinia xanthochymus.

摘要

This project studies the diverse chemistry of the Clusiaceae especially Garcinia xanthochymus fruits. In addition, a comprehensive review of benzophenones isolated from angiosperms is also presented. The biosynthesis, sources, isolation, structural determination, and biological activities of benzophenones are explored in detail. Also, the activity-guided isolation and structural elucidation of xanthochymol by 1D and 2D NMR from Garcinia xanthochymus fruits is examined.; Fruits of five Clusiaceae species, Garcinia aristata, Garcinia livingstonei, Garcinia spicata, Rheedia edulis, and Rheedia gardneriana, were studied by LC-MS to prioritize them for further activity-guided isolation. In addition, a dereplication system using the on-line 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay is described.; A methanol extract of Garcinia xanthochymus fruits was subjected to activity-guided fractionation yielding two novel benzophenones, guttiferone H and gambogenone. Guttiferone H contains a 7-membered ring attached to the bicyclo[3.3.1]nonane system at positions 7 and 8 and the B/C-ring system in gambogenone is a novel bicyclo[3.3.2]decane system. Both novel compounds displayed cytotoxicity in the SW-480 colon cancer cell line with IC50 = 12 and 188 muM, respectively. In addition, both guttiferone H and gambogenone induced apoptosis in SW-480 colon cancer cells. Both guttiferone H and gambogenone displayed antioxidant activity in the DPPH assay with IC 50 = 64 and 38.7 muM, respectively.; Eleven known compounds, aristophenone A, alloathyriol, amentoflavone, 3,8″-biapigenin, cycloxanthochymol, (+/-)-fukugetin, (+/-)-fukugiside, guttiferone E, isoxanthochymol, (+/-)-volkensiflavone, and xanthochymol were also obtained. All eleven known compounds were tested in the SW-480 colon cancer and the DPPH assays. As a group the known benzophenones displayed potent cytotoxicity in the SW-480 colon cancer cell assay (IC 50 = 7.5--33.3 muM) and antioxidant activity in the DPPH assay, IC50 = 53--73 muM. The biflavonoids were less active in both assays, (SW-480, IC50 = 111--200 muM; DPPH, IC 50 = 62--400 muM). The xanthone alloathyriol was not active in the DPPH assay and displayed cytotoxicity in the SW-480 assay, IC50 = 117 muM.; In summary, six Clusiaceae species were analyzed for their phytochemical constituents and a number of novel and known benzophenones, biflavonoids, and xanthones were identified and isolated from Garcinia xanthochymus fruits.