The evaluation of metal co-ordinating Bis-Thiosemicarbazones as potential anti-malarial Agents

Fady N. Akladios, Scott D. Andrew, Samantha J. Boog, Carmen de Kock, Richard K. Haynes, Christopher J. Parkinson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)51-58
Number of pages8
JournalMedicinal chemistry (Shariqah (United Arab Emirates))
Volume15
Issue number1
DOIs
Publication statusPublished - 01 Jan 2019

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