title: Synthesis and antimalarial activity of trioxaquine derivatives.
abstract: Trioxaquines are dual molecules that contain a trioxane motif linked to an aminoquinoline entity. Among the different compounds of this series, trioxaquine cis-15 (DU1302 c), prepared from alpha-terpinene, a cheap natural product, showed efficient antimalarial activity in vitro on both sensitive and resistant strains of Plasmodium falciparum (IC(50)=5-19 nM). A stereochemical description of this stable, nontoxic, and non-genotoxic antimalarial agent is detailed. Mice infected with P. vinckei were successfully treated with cis-15 in a four-day suppressive test. The doses required to decrease parasitemia by 50 % (ED(50)) were 5 and 18 mg kg(-1) d(-1) after intraperitoneal and oral administration, respectively. Parasitemia clearance was complete without recrudescence at an intraperitoneal dose of 20 mg kg(-1) d(-1).
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Dechy-Cabaret
authors.forename: Françoise
authors.initials: F
authors.lastname: Benoit-Vical
authors.forename: Christophe
authors.initials: C
authors.lastname: Loup
authors.forename: Anne
authors.initials: A
authors.lastname: Robert
authors.forename: Heinz
authors.initials: H
authors.lastname: Gornitzka
authors.forename: Anne
authors.initials: A
authors.lastname: Bonhoure
authors.forename: Henri
authors.initials: H
authors.lastname: Vial
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Magnaval
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Séguéla
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data; D004351:Drug Resistance; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D018512:Parasitemia / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D019086:Bridged Bicyclo Compounds, Heterocyclic; C433786:DU 1102; C497428:DU1112; C497429:DU1114; C497427:DU1302c