Antimalarial Natural Products from Terrestrial Macrofungi
File version
Author(s)
Primary Supervisor
Quinn, Ronald
Andrews, Katherine
Davis, Rohan
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
Abstract
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.
Journal Title
Conference Title
Book Title
Edition
Volume
Issue
Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Biomolecular and Physical Sciences
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Note
Access the data
Related item(s)
Subject
Malaria
Antimalarial drugs
Macrofungi