Antimalarial Natural Products from Terrestrial Macrofungi
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Although global cases and death from malaria have reduced over the last ten years, malaria is still a significant infectious disease. This disease kills about 2000 people per day. There is currently no licenced vaccine and current drugs are failing due to parasite drug resistance. Thus, there is an urgent need to develop new drugs to prevent and treat this disease. Natural products and their derivatives have played a significant role in drug discovery, since they have been an important source or inspiration for numerous current drugs. Australian macrofungi have rarely been studied for their potential as sources of new bioactive natural products, and in the antimalarial drug discovery realm, this is a pioneering study. As part of a research program aimed at identifying new antimalarial lead compounds or drugs from nature, a pre-fractionated fungal library was screened for antimalarial activity. All macrofungi used during these studies were collected from a variety of ecosystems found within the state of Queensland, Australia. A taxonomically diverse set of fungi were used with 37 families and 62 genera represented. The library consisted of 2,035 fractions obtained from C18 HPLC fractionation of 407 DCM/MeOH fungal extracts, with five fractions collected for each extract. A radiometric growth inhibition assay was used to screen the fractions against the chloroquine sensitive Plasmodium falciparum 3D7 malaria parasite line. Of the 2,035 fractions screened, 20 displayed inhibition of >80% towards P. falciparum, the cut off selected for pursuing lead fractions. Bioassay- or UV-guided fractionations were performed on three fungal samples, and several antimalarial natural product compounds were purified and their chemical structures determined using a combination of 1D/2D NMR, MS, and UV data.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
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