Antigiardial activity of novel guanidine compounds

A.J. Stevens; R. Abraham; K.A. Young; C.C. Russell; S.N. McCluskey; J.R. Baker; B. Rusdi; S.W. Page; R. O'Handley; M. O'Dea; S. Abraham; A. McCluskey

doi:10.1002/cmdc.202200341

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Antigiardial activity of novel guanidine compounds

Journal article

Peer reviewed

Antigiardial activity of novel guanidine compounds

A.J. Stevens, R. Abraham, K.A. Young, C.C. Russell, S.N. McCluskey, J.R. Baker, B. Rusdi, S.W. Page, R. O'Handley, M. O'Dea, …

ChemMedChem, Vol.17(21), e202200341

2022

DOI: https://doi.org/10.1002/cmdc.202200341

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Abstract

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.

Details

Title: Antigiardial activity of novel guanidine compounds
Authors/Creators: A.J. Stevens (Author/Creator) - University of Newcastle Australia
R. Abraham (Author/Creator) - Murdoch University
K.A. Young (Author/Creator) - University of Newcastle Australia
C.C. Russell (Author/Creator) - University of Newcastle Australia
S.N. McCluskey (Author/Creator) - University of Newcastle Australia
J.R. Baker (Author/Creator) - University of Newcastle Australia
B. Rusdi (Author/Creator) - Murdoch University
S.W. Page (Author/Creator) - Neoculi Pty Ltd Commercialisation AUSTRALIA
R. O'Handley (Author/Creator)
M. O'Dea (Author/Creator)
S. Abraham (Author/Creator) - Murdoch University
A. McCluskey (Author/Creator) - University of Newcastle Australia
Publication Details: ChemMedChem, Vol.17(21), e202200341
Publisher: John Wiley and Sons Ltd
Identifiers: 991005539995607891
Copyright: © 2022 The Authors.
Murdoch Affiliation: Antimicrobial Resistance and Infectious Disease Laboratory; Harry Butler Institute
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.246 Diarrheal Diseases; 1.246.985 Cryptosporidium
Web Of Science research areas: Chemistry, Medicinal; Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology