TY - BOOK
T1 - An evolutionary perspective on drug discovery in the plant genus Euphorbia L. (Euphorbiaceae)
AU - Ernst, Madeleine
PY - 2017
Y1 - 2017
N2 - Plants have been widely used in many traditional medical systems around the world and are still thesource of many modern drugs. However, the rate at which new plant-derived drugs are discoveredis slow and recent estimates of biodiversity loss, as well as the need for tackling global healthcarethreats, urge for systematic and time-efficient approaches in finding new drug candidates. Manydrugs are derived from plant specialized metabolites, chemical compounds, which are synthesizedby the plants in response to evolutionary adaptation to environmental and ecological factors, for example,to combat herbivory and physical stresses or to attract pollinators. Consequently, specializedmetabolites, as well as plants used in traditional medicine, are not randomly distributed across phylogenetictrees. Evolutionary approaches to plant-based drug discovery suggest that this informationcan be used to guide the search for new plant-derived drugs, in particular by systematizing speciesselection. The genus Euphorbia is among the largest genera of flowering plants with an almost cosmopolitandistribution. Its species richness and remarkable diversity in growth forms have made it amodel group for understanding plant evolution and diversification. Also, Euphorbia species producean often chemically highly diverse latex exhibiting an exceptional number of biological activities withpharmaceutical interest. In this PhD project, the genus Euphorbia was chosen as a model group forstudying evolutionary approaches to plant-based drug discovery. Phylogenetic patterns in speciesused in traditional medicine were investigated, and it was found that species used medicinally are notrandomly distributed across the phylogenetic tree. Subsequently, Euphorbia chemical diversity andbioactivity were investigated using mass spectral molecular networking, 3D mass spectral imagingas well as high-resolution bioactivity profiling in cell-based high-throughput screening assays of agenus-wide representative subset of over 40 species sampled from the Botanical Garden in Copenhagen.More than 600 specialized metabolites could be putatively identified and for the first timetheir genus-wide distribution as well as evolutionary drivers of the chemical diversity in Euphorbiacould be assessed. The pharmaceutically highly relevant Euphorbia diterpenoids were found to bestructurally most diverse in species native to Europe, Africa, and Asia compared to species native tothe Americas. It is hypothesized that these species are subject to a coevolutionary plant-herbivorearms race, leading to more diverse and biologically active molecules.
AB - Plants have been widely used in many traditional medical systems around the world and are still thesource of many modern drugs. However, the rate at which new plant-derived drugs are discoveredis slow and recent estimates of biodiversity loss, as well as the need for tackling global healthcarethreats, urge for systematic and time-efficient approaches in finding new drug candidates. Manydrugs are derived from plant specialized metabolites, chemical compounds, which are synthesizedby the plants in response to evolutionary adaptation to environmental and ecological factors, for example,to combat herbivory and physical stresses or to attract pollinators. Consequently, specializedmetabolites, as well as plants used in traditional medicine, are not randomly distributed across phylogenetictrees. Evolutionary approaches to plant-based drug discovery suggest that this informationcan be used to guide the search for new plant-derived drugs, in particular by systematizing speciesselection. The genus Euphorbia is among the largest genera of flowering plants with an almost cosmopolitandistribution. Its species richness and remarkable diversity in growth forms have made it amodel group for understanding plant evolution and diversification. Also, Euphorbia species producean often chemically highly diverse latex exhibiting an exceptional number of biological activities withpharmaceutical interest. In this PhD project, the genus Euphorbia was chosen as a model group forstudying evolutionary approaches to plant-based drug discovery. Phylogenetic patterns in speciesused in traditional medicine were investigated, and it was found that species used medicinally are notrandomly distributed across the phylogenetic tree. Subsequently, Euphorbia chemical diversity andbioactivity were investigated using mass spectral molecular networking, 3D mass spectral imagingas well as high-resolution bioactivity profiling in cell-based high-throughput screening assays of agenus-wide representative subset of over 40 species sampled from the Botanical Garden in Copenhagen.More than 600 specialized metabolites could be putatively identified and for the first timetheir genus-wide distribution as well as evolutionary drivers of the chemical diversity in Euphorbiacould be assessed. The pharmaceutically highly relevant Euphorbia diterpenoids were found to bestructurally most diverse in species native to Europe, Africa, and Asia compared to species native tothe Americas. It is hypothesized that these species are subject to a coevolutionary plant-herbivorearms race, leading to more diverse and biologically active molecules.
UR - https://rex.kb.dk/primo-explore/fulldisplay?docid=KGL01010656706&context=L&vid=NUI&search_scope=KGL&isFrbr=true&tab=default_tab&lang=da_DK
M3 - Ph.D. thesis
BT - An evolutionary perspective on drug discovery in the plant genus Euphorbia L. (Euphorbiaceae)
PB - Natural History Museum of Denmark, Faculty of Science, University of Copenhagen
ER -