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

Holloway, Georgina A.; Parisot, John P; Novello, Patrizia M; Watson, Keith G.; Armstrong, T. P.; Thompson, R.C.A.; Street, Ian P.; Baell, Jonathan B.

doi:10.1016/j.bmcl.2010.02.022

Cited by 6 publications

(1 citation statement)

References 7 publications

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“…The antiplasmodial activity increases with the halogen atom in ortho position whereas for T. b. brucei, the para position is the most appropriate for activity. In addition compounds with heavy halogens, like iodine or bromine, are more potent against T. b. brucei which may suggest a combination of electronegativity and hydrophobicity for antitrypanosomal activity, as previously mentioned in the literature for T. cruzi [15]. 3α-(2'-Chlorobenzoyloxy)tropane 4 showed the most promising activity against Plasmodium falciparum.…”

Section: Discussionsupporting

confidence: 59%

Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis

Cretton¹,

Bartholomeusz²,

Mehl³

et al. 2014

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A series of twelve analogs carrying fluoro, chloro, bromo and iodo halogens on the ortho, meta and para positions of a benzoyloxytropane skeleton were synthesized by a simple acylation of 8-methyl-8-aza-bicyclo[3.2.1]octan- 3α-ol by halogenobenzoyl chlorides. The compounds were evaluated in vitro against Plasmodium falciparum (P. f.), Trypanosoma brucei brucei (T. b. b.), Trypanosoma cruzi (T. c.) and Leishmania infantum (L. i.). This study shows that the presence of a halogenated atom and its position on the aromatic ring are important for in vitro activity. Compounds 4 (IC50 = 3.6 µM), 8 (IC50 = 6.7 µM), 5 (IC50 = 8.1 µM) and 7 (IC50 = 9.5 µM) were found the most active against P. f., whereas compounds 12 (IC50 = 5.1 µM), 11 (IC50 = 5.6 µM) and 9 (IC50 = 5.8 µM) exhibited the most pronounced activity against T. b. b. This series of compounds can be considered as non-toxic to the human cell line MRC-5.

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Section: Discussionsupporting

confidence: 59%

Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis

Cretton¹,

Bartholomeusz²,

Mehl³

et al. 2014

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ChemInform Abstract: Discovery of Novel and Potent Benzhydryl‐Tropane Trypanocides Highly Selective for Trypanosoma cruzi.

et al. 2010

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-Replacement of the aryl chloride substituent with chloro homologues in a previously identified potent benzhydryl tropinone oxime leads to the discovery of analogues (I) which reveal better activity than the original hit (Ic) has an EC50 against T. cruzi of 30 nM and a cytotoxicity selectivity index of >1000 relative to rat sheletal myoblast L-6 cells. A combination of electronegativity and hydrophobicity seems to be important for potent activity. -(HOLLOWAY, G. A.; PARISOT, J. P.; NOVELLO, P. M.; WATSON, K. G.; ARMSTRONG, T.; THOMPSON, R. C. A.; STREET, I. P.; BAELL*, J. B.; Bioorg. Med.

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First Acid‐Catalyzed Entry to O‐Alkylated Hydroximides from Benzylic Alcohols

et al. 2011

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

Cited by 6 publications

References 7 publications

Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis

Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis

ChemInform Abstract: Discovery of Novel and Potent Benzhydryl‐Tropane Trypanocides Highly Selective for Trypanosoma cruzi.

First Acid‐Catalyzed Entry to O‐Alkylated Hydroximides from Benzylic Alcohols

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