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

Keenan, M., Chaplin, J.H., Alexander, P.W., Abbott, M.J., Best, W. M., Khong, A., Botero Gomez, A., Perez, C.J., Cornwall, S., Thompson, R.C.A., White, K.L., Shackleford, D.M., Koltun, M., Chiu, F.C.K., Morizzi, J., Ryan, E., Campbell, M., von Geldern, T.W., Scandale, I., Chatelain, E. and Charman, S.A. (2013) Two analogues of fenarimol show curative activity in an experimental model of chagas disease. Journal of Medicinal Chemistry, 56 (24). pp. 10158-10170.

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

Item Type:	Journal Article
Murdoch Affiliation:	School of Veterinary and Life Sciences
Publisher:	American Chemical Society
Copyright:	© 2013 American Chemical Society.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/20436

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