Using a phylogenetic approach to selection of target plants in drug discovery of acetylcholinesterase inhibiting alkaloids in Amaryllidaceae tribe Galantheae

We present phylogenetic analyses of 32 taxa of Amaryllidaceae tribe Galantheae, 6 taxa of other Eurasian genera of Amaryllidaceae and Phaedranassa dubia as outgroup in order to provide a phylogenetic framework for selection of candidate plants for lead discovery in relation to Alzheimer’s disease. We used DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) and the plastid matK and trnL-F regions. Phylogenetic analyses using maximum parsimony and Bayesian inference strongly support a monophyletic tribe Galantheae in a narrow sense, including only Acis, Galanthus and Leucojum. Infrageneric relationships of Galanthus only partly support previous classifications. Alkaloid profiles and inhibition of acetylcholinesterase (AChE) were investigated for 18 taxa using gas chromatography–mass spectrometry (GC–MS) and an assay measuring inhibition of AChE activity. AChE inhibitory activity was found in all investigated clades and was correlated with alkaloid profiles of the plants. Lowest IC50 values were expressed by extracts containing either galanthamine or lycorine type compounds. Evaluation of available chemistry and activity data in a phylogenetic framework could be used to select target species for further investigation.

Research highlights
► Phylogenetic analyses strongly support a monophyletic tribe Galantheae in a narrow sense, including only Acis, Galanthus and Leucojum.
► Infrageneric relationships of Galanthus only partly support previous classifications.
► Acetylcholinesterase inhibitory activity is found in all investigated clades and is correlated with alkaloid profiles of the plants.
► The strongest acetylcholinesterase inhibitory activity is expressed by extracts containing either galanthamine or lycorine type compounds.
► Simultaneous evaluation of bioactivity and alkaloid profiles in a phylogenetic framework can potentially be used as selection tool in drug discovery.