Isolation Of PPBS-like Components From P. Chinensis And Structural Optimization Of A Novel Wnt Signaling Pathway Activator

Objectives:To isolate compounds of polyprenylated benzophenones(PPBS)fromthe leaves and twigs of Garciniamultiflora and find PPBS type compounds with considerable bioactivities. To modify the structure of curcumol, which is a small molecular compound proved to be a Wnt/β-catenin signaling pathway agonist. After measuring the Wnt/β-catenin signaling pathway activity of these synthesized derivatives, we hope to identifystrongeractive derivatives and discuss the structure-activity relationship of curcumol,which could helpus tofurther study of mechanism of its effects of Wnt/β-catenin signaling pathway.Method: 1.Isolation,purification and structural elucidation ofcompounds fromthe leaves and twigs of Garciniamultifloraby using a multitude of chromatography technologies as well as various spectroscopic methods(NMR, MS, UV, IR, CD, et al.). 2. Measured the bioactivity of isolated compound by cytotoxicity bioassays, inhibition of Nitric Oxide production assay, and lysosomal acidification assay.3. Isolated and purified Curcumol from ezhu oil by silica gel column chromatography and recrystallization.4. Derivatives ofcurcumol were prepared and measured the activity of Wnt/β-catenin signaling pathway.Result: 1.Thirteen compounds, including three novel oneswith new structuralskeleton, were isolated by silica gel column chromatography and HPLC from the leaves and twigs of Garcinia multiflora. Their structures were identified as(+)-garcimulin A,(-)-garcimulin A, garcimulin B, sampsonione L, hyperibone G, isogarcinol, xanthochymol, garcicowin C, garcinialone, clovane-2,9-diol, isopimpinellin, 1,6-dihydroxy-3, 7-dimethoxyxanthone andβ-sitosterol, respectively. Among them,(+)-Garcimulin A,(-)-garcimulin A andgarcimulin B were three novel oneswith new structuralskeleton. Moreover,(+)-garcimulin A and(-)-garcimulin A were isolated as a pair of enantiomers of PPBSfor the first time. It wasidentifiedthat the acidification of lysosomes in He La cellwas obviously affected by one of the PPBS compound for the first time. 2. 17 curcumol derivatives were synthesized including 10 new structures. Furthermore, all the derivatives were evaluated activate activity of Wnt/β-catenin signaling pathway. The results suggested that the hemigetalmoietyin curcumol iscritical and the C-C double bound was not essential for its bio-activity. The new derivative with a Biotin moietywas also identified as anagonist of Wnt/β-catenin signaling pathway, which would be a chemical proobe of the mechanism study of activating Wnt/β-catenin signaling pathway.