A Grand Challenge. 3. Unbiased Phenotypic Function Of Metabolites From Australia Plants Gloriosa Superba And Alangium Villosum Against Parkinson'S Disease

As part of a continuing research program aiming to identify chemical probes to interrogate Parkinson's disease (PD), we have investigated the Australian plants Gloriosa superba and Alangium villosum. The chemical investigations of G. superba resulted in the isolation of four new alkaloids, beta-lumicolchicosides A-C (1-3) and gamma-lumicolchicoside A (4), together with four lumicolchicine derivatives (5-8) and six colchicine analogues (9-14) as known structures. The chemical investigations of A. villosum resulted in the isolation of four new benzoquinolizidine N-oxides, tubulosine N-beta(5)-oxide (15), isotubulosine N-alpha(5)-oxide (16), 9-demethyltubulosine N-beta(5)-oxide (17), and 9-demethylisotubulosine N-alpha(5)-oxide (18), together with five known benzoquinolizidine alkaloids (19-23). The chemical structures of the new compounds (1-4 and 15-18) were characterized unambiguously by extensive analysis of their NMR and MS data. Unbiased multidimensional profiling was used to investigate the phenotypic profiles of all of the metabolites. The results show that the lead probes have different effects on cellular organelles that are implicated in PD in patient-derived cells.