Abstract

This research project involves the chemical profiling of anti-Alzheimer’s active compounds from the Fijian plant, Ficus barclayana using advanced chromatography, mass spectrometry and NMR techniques. A potentially new compound with possible anti-Alzheimer’s properties has been previously isolated from Ficus barclayana, which has been shown to reduce tau protein aggregation. Tau protein aggregation in the brain is a hall mark of Alzheimer’s disease. The compound which has never been identified was initially extracted and isolated from the plant using methanol and dichloromethane, and semi-purified using a modified Kupchan1 liquid-liquid partitioning scheme, with further purifications by HPLC and analysed by HR-LCMS and NMR. Due to low amount of sample, the compound could not be identified. This work is a follow up of that initial project where extracts from the same plant genus have been received from the Fiji Islands and was repurified using bioassay guided fractionation to get the target compounds in good yield so that structural analysis and tau-aggregation inhibition assays can be completed. Tau aggregation inhibition assay was carried out at Tau Rx Therapeutics, Aberdeen. There was a total of 382 masses found from the Kupchan fractions of FH, FD, FM, WW and WB, and 88 masses found in the pure compounds, which had a quality score of more than 40%, as shown in the appendix section Table A16-A19. Six compounds showed activity for the anti-cancer and anti-Alzheimer's screening, as shown in Chapter 4 in Tables 3 and 4, with compound FH5 being the most active. Two compounds were dereplicated through 1D and 2D NMR analysis with a partial structure proposed as shown in Chapter 4 as Figures 33 & 34. Further purification methods, such as HPLC, need to be performed to determine the complete structures of these compounds.