Journal article
Analogues of Fenarimol are potent inhibitors of Trypanosoma cruzi and are efficacious in a murine model of Chagas Disease
Journal of Medicinal Chemistry, Vol.55(9), pp.4189-4204
2012
Abstract
We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC 50s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
Details
- Title
- Analogues of Fenarimol are potent inhibitors of Trypanosoma cruzi and are efficacious in a murine model of Chagas Disease
- Authors/Creators
- M. Keenan (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaM.J. Abbott (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaP.W. Alexander (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaT. Armstrong (Author/Creator) - Murdoch UniversityW.M. Best (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaB.M. Berven (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaA. Botero Gomez (Author/Creator)J.H. Chaplin (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaS.A. Charman (Author/Creator) - Monash UniversityE. Chatelain (Author/Creator) - Drugs for Neglected Diseases InitiativeT.W. von Geldern (Author/Creator) - Drugs for Neglected Diseases InitiativeM. Kerfoot (Author/Creator) - Murdoch UniversityA. Khong (Author/Creator) - Murdoch UniversityT. Nguyen (Author/Creator) - Monash UniversityJ.D. McManus (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaJ. Morizzi (Author/Creator) - Monash UniversityE. Ryan (Author/Creator) - Monash UniversityI. Scandale (Author/Creator) - Drugs for Neglected Diseases InitiativeR.A. Thompson (Author/Creator)S.Z. Wang (Author/Creator) - Epichem Pty Ltd, South Street, Murdoch, WA 6150, AustraliaK.L. White (Author/Creator) - Monash University
- Publication Details
- Journal of Medicinal Chemistry, Vol.55(9), pp.4189-4204
- Publisher
- American Chemical Society
- Identifiers
- 991005541279907891
- Copyright
- © 2012 American Chemical Society
- Murdoch Affiliation
- School of Veterinary and Biomedical Sciences
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.261 Parasitology - Trypanosoma & Leishmania
- 1.261.596 Trypanosoma Biology
- Web Of Science research areas
- Chemistry, Medicinal
- ESI research areas
- Chemistry