Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi
- Author(s)
- Holloway, GA; Parisot, JP; Novello, PM; Watson, KG; Armstrong, T; Thompson, RCA; Street, IP; Baell, JB;
- Details
- Publication Year 2010-03-15,Volume 20,Issue #6,Page 1816-1818
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
- Publication Type
- Journal Article
- Abstract
- A benzhydryl tropinone oxime that is potently toxic to Trypanosoma cruzi has been previously identified. An SAR investigation determined that no part of the original compound was superfluous and all early SAR probes led to significant drops in activity. The only alteration that could be achieved without loss of activity was replacement of the aryl chloride substituent with chloro homologues. This led to the discovery of a trifluoromethyl-containing analogue with an EC(50) against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells. (C) 2010 Elsevier Ltd. All rights reserved.
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- CHAGAS-DISEASE; INHIBITORS; CHEMOTHERAPY
- Publisher's Version
- https://doi.org/10.1016/j.bmcl.2010.02.022
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-03-15 12:00:00