Aminoguanidines: new leads for treatment of Giardia duodenalis infection
Date
2019
Authors
Abraham, R.J.
Abraham, S.
Stevens, A.J.
Page, S.W.
McCluskey, A.
Trott, D.J.
O'Handley, R.M.
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Journal article
Citation
International Journal for Parasitology: Drugs and Drug Resistance, 2019; 10:38-44
Statement of Responsibility
Rebecca J. Abraham, Sam Abraham, Andrew J. Stevens, Stephen W. Page, Adam McCluskey, Darren J. Trott, Ryan M. O'Handley
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Abstract
Giardia duodenalis is an ubiquitous parasitic pathogen that causes significant morbidity and mortality worldwide. Failures in drug therapy are commonly due to poor patient compliance as a result of the need for repeated administration, off target drug effects and increasing parasite drug resistance. In this study the in vitro efficacy and selectivity of the aminoguanidine compound robenidine and 2 structural analogues against Giardia were determined. After 5 h exposure to each compound the IC₅₀ was as low as 0.2 μM with corresponding MLCs as low as 2.8 μM. This is in contrast to metronidazole which required 24 h to exhibit inhibitory activity. A modified adherence assay, developed for this study, demonstrated that three of the compounds inhibited in vitro adherence of the parasite. The lead compound exhibited rapid giardicidal activity (<5hr). In addition, microscopy studies demonstrated damage to the plasma membrane of trophozoites. In conclusion, a class of aminoguanidines, represented by robenidine, has shown antigiardial activity warranting further investigation.
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© 2019 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).