CYRTANTHUS-DRUGS · the predictive power of phylogenies in plant drug discovery - a case study of the genus Cyrtanthus (Amaryllidaceae)

The predictive power of phylogenies in plant drug discovery - a case study of the genus Cyrtanthus (Amaryllidaceae)

During evolution, organisms such as plants have developed a diversity of chemical defences, leading to the evolution of various groups of specialised metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive approach enabling more efficient selection of plants for traditional medicine and lead discovery. However, this relationship has rarely been rigorously tested and the potential predictive power is thus unknown. We originally proposed to investigate the predictive power of phylogenies in plant drug discovery by exploring and comparing biological activity and chemistry of plants in the genus Cyrtanthus (Amaryllidaceae family) from southern Africa. However it was soon realised that a single genus was too narrow and so we extended our project to include other Amaryllidaceae. An additional project that was aimed at developing a phylogenetic hypothesis for the important medicinal and horticultural genus Tulbaghia (Allioideae) was also initiated. Like other members of the Allioideae, Tulbaghia are known to contain various sulfur compounds that exhibit prominent physiological properties, including antimicrobial, antiinflammatory, antithrombotic, hypolipidemic, and blood-pressure lowering activity. The precursors of these biologically active compounds are various S-substituted cysteine derivatives. Upon tissue disruption, these sulfur amino acids are enzymatically cleaved to yield a wide variety of compounds, including pungent thiosulfinates and lachrymatory sulfines. This postdoctoral fellowship consisted of a 24 months incoming phase at the Natural Products Research Laboratory, Department of Medicinal Chemistry, and the Natural History Museum of Denmark, University of Copenhagen, Denmark (University of Copenhagen, host institution). We produced a phylogenetic hypothesis for the medicinally important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over 100 species. We tested if alkaloid diversity and central nervous system related activities are significantly correlated with phylogeny. Several Amaryllidoideae genera are non-monophyletic emphasising the importance of using phylogeny for interpretation of character distribution. Alkaloid diversity, in vitro inhibition of acetylcholinesterase (AChE, important in the treatment of the symptoms of Alzheimer's disease) and binding to the serotonin reuptake transporter (SERT, important in the treatment of depression) are significantly correlated with phylogeny. This has implications for the use of phylogenies to interpret chemical evolution and biosynthetic pathways, to select candidate taxa for lead discovery, and to make recommendations for traditional use and conservation priorities.

Data: CORDIS, © European Union