Catalog Home Page

Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi

Holloway, G.A., Parisot, J.P., Novello, P.M., Watson, K.G., Armstrong, T., Thompson, R.C.A., Street, I.P. and Baell, J.B. (2010) Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi. Bioorganic & Medicinal Chemistry Letters, 20 (6). pp. 1816-1818.

[img]
Preview
PDF - Authors' Version
Download (559kB) | Preview
    Link to Published Version: http://dx.doi.org/10.1016/j.bmcl.2010.02.022
    *Subscription may be required

    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 EC50 against T. cruzi of 30 nM and a cytotoxicity selectivity index of over 1000 relative to rat skeletal myoblast L-6 cells.

    Publication Type: Journal Article
    Murdoch Affiliation: School of Veterinary and Biomedical Sciences
    Publisher: Elsevier BV
    Copyright: © 2010 Elsevier Ltd.
    URI: http://researchrepository.murdoch.edu.au/id/eprint/3765
    Item Control Page

    Downloads

    Downloads per month over past year