title: Synthesis and in vitro evaluation of tropane halogenated-derivatives against malaria, sleeping sickness, Chagas disease and leishmaniasis.
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.
authors.forename: Sylvian
authors.initials: S
authors.lastname: Cretton
authors.forename: Trixie A
authors.initials: TA
authors.lastname: Bartholomeusz
authors.forename: Florence
authors.initials: F
authors.lastname: Mehl
authors.forename: Yves
authors.initials: Y
authors.lastname: Allenbach
authors.forename: An
authors.initials: A
authors.lastname: Matheeussen
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest- Ansermet 30, CH-1211 Geneva 4, Switzerland. philippe.christen@unige.ch.
authors.forename: Philippe
authors.initials: P
authors.lastname: Christen
mesh_terms: D000215:Acylation; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects / Q000254:growth & development; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000254:growth & development; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
chemical_list: D000962:Antimalarials; D000981:Antiprotozoal Agents; D014326:Tropanes; D014344:Trypanocidal Agents