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

G.A. Holloway; J.P. Parisot; P.M. Novello; K.G. Watson; T. Armstrong; R.C.A. Thompson; I.P. Street; J.B. Baell

doi:10.1016/j.bmcl.2010.02.022

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

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

G.A. Holloway, J.P. Parisot, P.M. Novello, K.G. Watson, T. Armstrong, R.C.A. Thompson, I.P. Street and J.B. Baell

Bioorganic & Medicinal Chemistry Letters, Vol.20(6), pp.1816-1818

2010

DOI: https://doi.org/10.1016/j.bmcl.2010.02.022

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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.

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Title: Discovery of novel and potent benzhydryl-tropane trypanocides highly selective for Trypanosoma cruzi
Authors/Creators: G.A. Holloway (Author/Creator)
J.P. Parisot (Author/Creator)
P.M. Novello (Author/Creator)
K.G. Watson (Author/Creator)
T. Armstrong (Author/Creator)
R.C.A. Thompson (Author/Creator)
I.P. Street (Author/Creator)
J.B. Baell (Author/Creator)
Publication Details: Bioorganic & Medicinal Chemistry Letters, Vol.20(6), pp.1816-1818
Publisher: Elsevier BV
Identifiers: 991005540553607891
Copyright: © 2010 Elsevier Ltd.
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.261 Parasitology - Trypanosoma & Leishmania; 1.261.596 Trypanosoma Biology
Web Of Science research areas: Chemistry, Medicinal; Chemistry, Organic
ESI research areas: Chemistry