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

M. Keenan, J.H. Chaplin, P.W. Alexander, M.J. Abbott, W.M. Best, Andrea Khong, A.M.C. Botero, C.J. Perez, S.M. Cornwall, R.A. Thompson, K.L. White, D.M. Shackleford, M. Koltun, F.C.K. Chiu, J. Morizzi, E.W. Ryan, M. Campbell, T.W. Von Geldern, I. Scandale, E. ChatelainS.A. Charman

    Research output: Contribution to journalArticle

    31 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. © 2013 American Chemical Society.
    Original languageEnglish
    Pages (from-to)10158-10170
    JournalJournal of Medicinal Chemistry
    Volume56
    Issue number24
    DOIs
    Publication statusPublished - 2013

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