Medicinal Chemistry

Atta-ur-Rahman  
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK
Email: mc@benthamscience.org

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

Author(s): Sylvian Cretton, Trixie A. Bartholomeusz, Florence Mehl, Yves Allenbach, An Matheeussen, Paul Cos, Louis Maes and Philippe Christen

Affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest- Ansermet 30, CH-1211 Geneva 4, Switzerland.

Keywords: Antiplasmodial activity, antitrypanosomal activity, cytotoxicity, halogenobenzoyl derivatives, tropane derivatives, tropine acylation.

Graphical Abstract:


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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Article Details

VOLUME: 10
ISSUE: 8
Page: [753 - 758]
Pages: 6
DOI: 10.2174/1573406410666140507095430