Design and synthesis of novel P. fulciparum GDH inhibitors for use as potential antimalarial agents

Kasonde, Edward Kumbirai (2021) Design and synthesis of novel P. fulciparum GDH inhibitors for use as potential antimalarial agents. Doctoral thesis, London Metropolitan University.


Malaria is a potentially fatal parasitic disease that is endemic in 109 countries and threatens over 2.4 billion people, representing 40% of the global population. While there has been a gradual decrease in the number of fatalities resulting from the disease in recent decades, this progress is now under serious risk of being reversed as a result of the parasite developing resistance to the currently available chemotherapies. This has led to a new impetus to look for new antimalarial drugs that have different modes of action to the ones that are currently available.

This thesis contains the following areas of research:

1) The design and synthesis of various compounds of the classes substituted benzyl-αhydroxy phosphonates, substituted benzyl-α-methylene phosphonates, substituted benzyl-α-hydroxy phosphonic acids and substituted benzyl-α-amino phosphonic acids. These compounds are intended to target one of the recently hypothesised antimalarial drug development targets, Pf-glutamate dehydrogenase (PfGDH).

2) The synthesised compounds were then tested for their antimalarial activity against the P. falciparum strains 3D7 and Dd2. Furthermore, the synthesised compounds were tested against other parasitic organisms, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major.

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