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dc.contributor.authorAkladios, Fady N.
dc.contributor.authorHaynes, Richard K.
dc.contributor.authorAndrew, Scott D.
dc.contributor.authorBoog, Samantha J.
dc.contributor.authorDe Kock, Carmen
dc.date.accessioned2019-02-28T09:10:00Z
dc.date.available2019-02-28T09:10:00Z
dc.date.issued2019
dc.identifier.citationAkladios, F.N. et al. 2019. The evaluation of metal co-ordinating bis-thiosemicarbazones as potential anti-malarial agents. Medicinal chemistry, 15(1):51-58. [https://doi.org/10.2174/1573406414666180525132204]en_US
dc.identifier.issn1573-4064
dc.identifier.issn1875-6638 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/31870
dc.identifier.urihttp://www.eurekaselect.com/162467
dc.identifier.urihttps://doi.org/10.2174/1573406414666180525132204
dc.description.abstractBackground: 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 antimalarialsen_US
dc.language.isoenen_US
dc.publisherBentham Scienceen_US
dc.subjectMalariaen_US
dc.subjectPlasmodiumen_US
dc.subjectThiosemicarbazoneen_US
dc.subjectMetal coordinationen_US
dc.subjectIronen_US
dc.subjectCopperen_US
dc.subjectReactive oxygenen_US
dc.titleThe evaluation of metal co-ordinating bis-thiosemicarbazones as potential anti-malarial agentsen_US
dc.typeArticleen_US
dc.contributor.researchID22966390 - Haynes, Richard Kingston


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