Plasmodium falciparum Plasmepsins IX and X: Structure- Function Analysis and the Discovery of New Lead Antimalarial drugs

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Author(s)
Primary Supervisor
Skinner-Adams, Tina
Brown, Chris
Other Supervisors
Gardiner, Donald
Year published
2014
Metadata
Show full item recordAbstract
Malaria is a deadly parasitic infection that poses an enormous threat to global health. While drugs are available, all of our current antimalarials are being gradually rendered ineffective by spreading drug resistance. Reports of increasing tolerance to artemisinin combination therapies, our most potent antimalarial treatments, are particularly concerning. To combat this problem there is an urgent need to identify new and unique targets within the malaria parasite against which novel chemotherapeutics can be developed. Studies investigating the antimalarial activity of HIV protease inhibitors (HIV PIs) have shown that these ...
View more >Malaria is a deadly parasitic infection that poses an enormous threat to global health. While drugs are available, all of our current antimalarials are being gradually rendered ineffective by spreading drug resistance. Reports of increasing tolerance to artemisinin combination therapies, our most potent antimalarial treatments, are particularly concerning. To combat this problem there is an urgent need to identify new and unique targets within the malaria parasite against which novel chemotherapeutics can be developed. Studies investigating the antimalarial activity of HIV protease inhibitors (HIV PIs) have shown that these drugs can inhibit the growth of Plasmodium in vitro, in vivo and ex vivo at clinically relevant concentrations. While the anti-parasitic action of these drugs is not fully understood, it is believed these agents inhibit the growth of parasites by targeting an essential malarial aspartic protease or plasmepsin (PM) and that these enzymes may represent new targets for drug development. The aim of this thesis was to investigate the Plasmodium falciparum aspartic proteases PM IX and X as potential new targets for antimalarial development.
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View more >Malaria is a deadly parasitic infection that poses an enormous threat to global health. While drugs are available, all of our current antimalarials are being gradually rendered ineffective by spreading drug resistance. Reports of increasing tolerance to artemisinin combination therapies, our most potent antimalarial treatments, are particularly concerning. To combat this problem there is an urgent need to identify new and unique targets within the malaria parasite against which novel chemotherapeutics can be developed. Studies investigating the antimalarial activity of HIV protease inhibitors (HIV PIs) have shown that these drugs can inhibit the growth of Plasmodium in vitro, in vivo and ex vivo at clinically relevant concentrations. While the anti-parasitic action of these drugs is not fully understood, it is believed these agents inhibit the growth of parasites by targeting an essential malarial aspartic protease or plasmepsin (PM) and that these enzymes may represent new targets for drug development. The aim of this thesis was to investigate the Plasmodium falciparum aspartic proteases PM IX and X as potential new targets for antimalarial development.
View less >
Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Biomolecular and Physical Sciences
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Subject
Malaria
Anti-malarial drugs
Plasmodium falciparum Plasmepsins IX and X