The evaluation of metal co-ordinating bis-thiosemicarbazones as potential anti-malarial agents
Date
2019Author
Akladios, Fady N.
Haynes, Richard K.
Andrew, Scott D.
Boog, Samantha J.
De Kock, Carmen
Metadata
Show full item recordAbstract
Background:
The emergence of resistance to the artemisinins which are the current mainstays for antimalarial chemotheraphy has created an environment where the development of new drugs acting in a mechanistally discrete manner is a priority.
Objective:
The goal of this work was to synthesize ane evaluate bis-thiosemicarbazones as potential antimalarial agents.
Methods: Fifteen compounds were generated using two condensation protocols and evaluated in vitro against the NF54 (CQ sensitive) strain of Plasmodium falciparum. A preliminary assessment of the potential for human toxicity was conducted in vitro against the MRC5 human lung fibroblast line.
Results:
The activity of the bis-thiosemicarbazones was highly dependent on the nature of the arene at the core of the structure. The inclusion of a non-coordinating benzene core resulted in inactive compounds, while the inclusion of a pyridyl core resulted in compounds of moderate or potent antimalarial activity (4 compounds showing IC50 < 250 nM).
Conclusion:
Bis-thiosemicarbazones containing a central pyridyl core display potent antimalarial activity in vitro. Sequestration and activation of ferric iron appears to play a significant role in this activity. Ongoing studies are aimed at further development of this series as potential antimalarials
URI
http://hdl.handle.net/10394/31870http://www.eurekaselect.com/162467
https://doi.org/10.2174/1573406414666180525132204
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- Faculty of Health Sciences [2386]