title: Antiprotozoal activity of ferroquine.
abstract: Ferroquine (FQ, SSR97193) is a synthetic compound currently in development for the treatment of malaria. The use of a single compound to treat several parasitoses would be very convenient for multi-infected patients and also for financial considerations. In this work, the activity of FQ was investigated on three other Protista parasites: Kinetoplastidae (Leishmania and Trypanosoma) and the cosmopolite parasite Trichomonas vaginalis. FQ exhibited a significant in vitro activity on Trypanosoma brucei brucei and Trypanosoma brucei gambiense, the agents of African trypanosomiasis in a range from 0.2 to 3.1 μM. In vivo, intraperitoneally administered FQ demonstrated a weak but significant trypanocidal activity at 100 μmol/kg, which is however higher than the maximum tolerated dose. The drop of the parasitemia of the treated mice was significantly related to the amount of injected FQ. Furthermore, this organometallic compound was responsible for a delay in the appearance of bloodstream parasites at 50 μmol/kg. However, it was not able to cure infected mice. Although no synergy was identified in vitro between FQ and pentamidine, these results justify further investigations by evaluating analogues in this chemical series.
authors.affiliation: Faculté de Pharmacie, UMR 8076 CNRS, Chimiothérapie Antiparasitaire, Univ. Paris-Sud, 92290 Châtenay-Malabry, France.
authors.forename: S
authors.initials: S
authors.lastname: Pomel
authors.forename: C
authors.initials: C
authors.lastname: Biot
authors.forename: C
authors.initials: C
authors.lastname: Bories
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D007891:Leishmania / Q000187:drug effects*; D000075163:Metallocenes; D051379:Mice; D021261:Parasitic Sensitivity Tests; D016896:Treatment Outcome; D014246:Trichomonas vaginalis / Q000187:drug effects*; D014345:Trypanosoma / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; C479230:ferroquine