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