title: New heterocyclic compounds: Synthesis and antitrypanosomal properties.
abstract: Three new series of quinoline, quinolone, and benzimidazole derivatives were synthesized and evaluated in vitro against Trypanosoma brucei gambiense. In the quinoline series, the metallo antimalarial drug candidate (ferroquine, FQ) and its ruthenium analogue (ruthenoquine, RQ, compound 13) showed the highest in vitro activities with IC50 values around 0.1 μM. Unfortunately, both compounds failed to cure Trypanosoma brucei brucei infected mice in vivo. The other heterocyclic compounds were active in vitro with IC50 values varying from 0.8 to 34 μM. One of the most interesting results was a fluoroquinolone derivative (compound 2) that was able to offer a survival time of 8 days after a treatment at the single dose of 100 μmol/kg by intraperitoneal route. Although no clear-cut structure-activity relationships emerged, further pharmacomodulations are worth to be developed in this series.
authors.affiliation: Univ. Paris-Sud, Faculté de Pharmacie, UMR 8076 CNRS, Chimiothérapie Antiparasitaire, 92290 Châtenay-Malabry, France.
authors.forename: S
authors.initials: S
authors.lastname: Pomel
authors.affiliation: Univ. Lille 1, UGSF, UMR 8576 CNRS, 59650 Villeneuve d'Ascq, France.
authors.forename: F
authors.initials: F
authors.lastname: Dubar
authors.affiliation: Laboratory of Organic Chemistry, Faculty of Sciences, University of Mons-UMONS, Mons, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Forge
authors.affiliation: Univ. Paris-Sud, Faculté de Pharmacie, UMR 8076 CNRS, Chimiothérapie Antiparasitaire, 92290 Châtenay-Malabry, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.affiliation: Univ. Lille 1, UGSF, UMR 8576 CNRS, 59650 Villeneuve d'Ascq, France. Electronic address: christophe.biot@univ-lille1.fr.
authors.forename: C
authors.initials: C
authors.lastname: Biot
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054879:Halogenation; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000075163:Metallocenes; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D000634:Aminoquinolines; D001562:Benzimidazoles; D005296:Ferrous Compounds; D006571:Heterocyclic Compounds; D000075163:Metallocenes; D011804:Quinolines; D015363:Quinolones; D014344:Trypanocidal Agents; C479230:ferroquine
keywords: Benzimidazole; Ferroquine; Quinoline; Quinolone; Sleeping sickness; Trypanosoma