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Aminoguanidines: New leads for treatment of Giardia duodenalis infection

Abraham, R.J., Abraham, S., Stevens, A.J., Page, S.W., McCluskey, A., Trott, D.J. and O'Handley, R.M. (2019) Aminoguanidines: New leads for treatment of Giardia duodenalis infection. International Journal for Parasitology: Drugs and Drug Resistance, 10 . pp. 38-44.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Publisher: Elsevier BV
Copyright: © 2019 Published by Elsevier Ltd on behalf of Australian Society for Parasitology
United Nations SDGs: Goal 3: Good Health and Well-Being
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