Abstract
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.
Keywords: Antiplasmodial activity, antitrypanosomal activity, cytotoxicity, halogenobenzoyl derivatives, tropane derivatives, tropine acylation.
Medicinal Chemistry
Title:Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis
Volume: 10 Issue: 8
Author(s): Sylvian Cretton, Trixie A. Bartholomeusz, Florence Mehl, Yves Allenbach, An Matheeussen, Paul Cos, Louis Maes and Philippe Christen
Affiliation:
Keywords: Antiplasmodial activity, antitrypanosomal activity, cytotoxicity, halogenobenzoyl derivatives, tropane derivatives, tropine acylation.
Abstract: 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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Cretton Sylvian, Bartholomeusz A. Trixie, Mehl Florence, Allenbach Yves, Matheeussen An, Cos Paul, Maes Louis and Christen Philippe, Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis, Medicinal Chemistry 2014; 10 (8) . https://dx.doi.org/10.2174/1573406410666140507095430
DOI https://dx.doi.org/10.2174/1573406410666140507095430 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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