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Antigiardial Activity of Novel Guanidine Compounds

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journal contribution
posted on 2025-05-09, 20:17 authored by Andrew J. Stevens, Rebecca Abraham, Kelly YoungKelly Young, Cecilia C. Russell, Adam McCluskeyAdam McCluskey, Jennifer BakerJennifer Baker, Bertha Rusdi, Stephen W. Page, Ryan O'Handley, Mark O'Dea, Sam Abraham
From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC50<5 μM, seven with IC50<1.0 μM. Most active were 2,2′-bis{[4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2′-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2′-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride (41) with IC50=0.2 μM. The maximal observed activity was a 5 h IC50 value of 0.2 μM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 μM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h.

Funding

ARC

LP110200770

History

Journal title

ChemMedChem

Volume

17

Issue

21

Article number

e202200341

Publisher

Wiley-Blackwell

Place published

Weinheim, Germany

Language

  • en, English

College/Research Centre

College of Engineering, Science and Environment

School

School of Environmental and Life Sciences

Rights statement

© 2022 The Authors. ChemMedChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. (http://creativecommons.org/licenses/by/4.0/).

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