Analogues of Fenarimol Are Potent Inhibitors of Trypanosoma cruzi and Are Efficacious in a Murine Model of Chagas Disease
Journal of Medicinal Chemistry2012Vol. 55(9), pp. 4189–4204
Citations Over TimeTop 10% of 2012 papers
Martine Keenan, Michael J. Abbott, Paul W. Alexander, T. P. Armstrong, Wayne M. Best, Bradley Berven, Adriana Botero, Jason H. Chaplin, Susan A. Charman, Eric Chatelain, Thomas W von Geldern, Maria Kerfoot, Andrea Khong, Tien Thuy Nguyen, Joshua D. McManus, Julia Morizzi, Eileen Ryan, Ivan Scandale, RC Andrew Thompson, Sen Z. Wang, Karen L. White
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(50)s 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.
Related Papers
- → Antichagasic Activities of Natural Products against Trypanosoma cruzi(2009)36 cited
- → Synthesis and Anti-Trypanosoma cruzi Activity of Diaryldiazepines(2014)22 cited
- → Looking for combination of benznidazole and Trypanosoma cruzi-triosephosphate isomerase inhibitors for Chagas disease treatment(2018)17 cited
- → Synthesis, Design, and Structure‐Activity Relationship of a Benzenesulfonylpiperazine Series against Trypanosoma cruzi(2022)11 cited
- → Specific Treatment For Trypanosoma Cruzi Infection (Chagas Disease)(2003)28 cited