Natural Product and Fragment-Based Drug Discovery Against Malaria Protein Targets by Native Mass Spectrometry

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Author(s)
Primary Supervisor
Quinn, Ronald
Brown, Christopher
Other Supervisors
Vu, Hoan
Year published
2017
Metadata
Show full item recordAbstract
Malaria control interventions have been effective in reducing malaria incidence and mortality rates globally over the last decade. However, increasing resistance of Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax), the two most prevalent parasite species, to the most used antimalarial drugs, threatens to halt the progress. Given the current limited arsenal of antimalarial drugs has been inspired by natural product scaffolds, these have the potential to be the source of new and structurally different antimalarial drugs, acting through novel mechanisms of action, that are urgently needed. Translating the ...
View more >Malaria control interventions have been effective in reducing malaria incidence and mortality rates globally over the last decade. However, increasing resistance of Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax), the two most prevalent parasite species, to the most used antimalarial drugs, threatens to halt the progress. Given the current limited arsenal of antimalarial drugs has been inspired by natural product scaffolds, these have the potential to be the source of new and structurally different antimalarial drugs, acting through novel mechanisms of action, that are urgently needed. Translating the structural and biologically relevant diversity of natural products into an efficient and effective drug development process is, nonetheless, not trivial. Fragment-based drug discovery (FBDD) is a relatively recent and promising approach for drug discovery. It involves the identification of small molecular weight compounds, called fragments, that weakly bind to a biological target and their elaboration through chemical synthesis to produce high affinity and selective drugs. For a rational and effective elaboration process, structural and thermodynamic information are essential.
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View more >Malaria control interventions have been effective in reducing malaria incidence and mortality rates globally over the last decade. However, increasing resistance of Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax), the two most prevalent parasite species, to the most used antimalarial drugs, threatens to halt the progress. Given the current limited arsenal of antimalarial drugs has been inspired by natural product scaffolds, these have the potential to be the source of new and structurally different antimalarial drugs, acting through novel mechanisms of action, that are urgently needed. Translating the structural and biologically relevant diversity of natural products into an efficient and effective drug development process is, nonetheless, not trivial. Fragment-based drug discovery (FBDD) is a relatively recent and promising approach for drug discovery. It involves the identification of small molecular weight compounds, called fragments, that weakly bind to a biological target and their elaboration through chemical synthesis to produce high affinity and selective drugs. For a rational and effective elaboration process, structural and thermodynamic information are essential.
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Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Natural Sciences
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Subject
Malaria control
Plasmodium falciparum (P. falciparum)
Plasmodium vivax (P. vivax)
Fragment-based drug discovery (FBDD)
Native mass spectrometry