Two analogues of fenarimol show curative activity in an experimental model of chagas disease

Martine Keenan, Jason Hugh Chaplin, Paul W Alexander, Michael J Abbott, Wayne Morris Best, Andrea Khong, Adriana Botero, Catherine Perez, Scott Cornwall, Richard Christopher Andrew Thompson, Karen Louise White, David Shackleford, Maria Koltun, Francis Chi Keung Chiu, Julia Morizzi, Eileen Ryan, Michael Campbell, Thomas W von Geldern, Ivan Scandale, Eric ChatelainSusan Ann Charman

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29 Citations (Scopus)

Abstract

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development.
Original languageEnglish
Pages (from-to)10158 - 10170
Number of pages13
JournalJournal of Medicinal Chemistry
Volume56
Issue number24
DOIs
Publication statusPublished - 2013

Cite this

Keenan, M., Chaplin, J. H., Alexander, P. W., Abbott, M. J., Best, W. M., Khong, A., ... Charman, S. A. (2013). Two analogues of fenarimol show curative activity in an experimental model of chagas disease. Journal of Medicinal Chemistry, 56(24), 10158 - 10170. https://doi.org/10.1021/jm401610c