Open Access Te Herenga Waka-Victoria University of Wellington
thesis_access.pdf (9.29 MB)

The Synthesis of Malonganenone Analogues for Antiparasitic Structure-Activity Relationship Analyses

Download (9.29 MB)
posted on 2021-12-09, 06:54 authored by Sarah AndreassendSarah Andreassend

The most lethal causative species of malaria, Plasmodium falciparum, has been reported as developing resistance against current antimalarial drugs in South-East Asia. New antimalarial drugs, especially those with novel modes of action, need to be established before resistance spreads.  The marine natural products malonganenones A, B, and C, isolated from the gorgonian Leptogorgia gilchristi, have recently been shown to inhibit P. falciparum parasite growth. Therefore, a library of malonganenone analogues were synthesised for structure activity relationship analysis. A range of purines, purinones, and pyrimidines were alkylated with simple terpenoid chains to generate malonganenone A and B analogues, while malonganenone C analogues were made by acetylation or formylation, then methylation of terpenoid amines.  The compounds were moderately active against P. falciparum infected red blood cells, but exhibited significant activity against Trypanosoma brucei, the parasite responsible for African sleeping sickness. Off target activity was assessed by assay against Escherichia coli, Staphylococcus aureus, Steptococcus uberis and HeLa cells. The overall structureactivity relationship analysis resulted in the identification of lead candidate, geranylgeranyl imidazole (146), which had IC50 values of 10.2 μM and 3.4 μM against P. falciparum and T. brucei, respectively.  In addition, the minimum inhibitory concentration of 146 against S. uberis and S. aureus was 16 – 32 μM and 128 μM, respectively. Compound 146 was inactive against E. coli and was also non-toxic to HeLa cells. In addition, a geometric mixture of E and Z isomers at the alkene closest to the imidazole head group was more active than just the E isomer as for 146, which suggested the Z isomer was more active than the E isomer. Therefore, the lead compound identified within this project was the 2Z isomer of geranylgeranyl imidazole.


Copyright Date


Date of Award



Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

Degree Discipline


Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level


Degree Name

Master of Science

ANZSRC Type Of Activity code

970103 Expanding Knowledge in the Chemical Sciences

Victoria University of Wellington Item Type

Awarded Research Masters Thesis



Victoria University of Wellington School

School of Chemical and Physical Sciences


Keyzers, Robert