title: In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives.
abstract: The effects of combining four dihydroethanoanthracenic (DEA) derivatives and chloroquine were assessed in vitro against Plasmodium falciparum chloroquine resistant parasites W2, Palo Alto, FCR3, and Bres1. Like verapamil or promethazine, the four dihydroethanoanthracenic derivatives tested can be added to the growing list of agents that show capability in enhancing the activity of chloroquine against resistant parasites. The structurally related tricyclic antihistaminic compounds examined in this study exerted different intrinsic antimalarial activity, but the same chloroquine-potentiating activity as verapamil or promethazine. They may act both on the rate of chloroquine accumulation and on its access to ferriprotoporphyrin IX. The reversal mechanism would be assumed to result from competition between DEA derivatives and chloroquine for efflux translocation sites, thus causing an increase in steady-state accumulation of chloroquine and a return to susceptibility. Restoration of therapeutic efficacy of chloroquine against resistant parasites by the administration of an additional drug available at relatively low cost may be a more effective strategy than the introduction of another antimalarial drug at the national level.
authors.affiliation: Unité de Parasitologie, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
authors.forename: Sandrine
authors.initials: S
authors.lastname: Alibert-Franco
authors.forename: Carole
authors.initials: C
authors.lastname: Houdoin
authors.forename: Joel
authors.initials: J
authors.lastname: Mosnier
authors.forename: Christiane
authors.initials: C
authors.lastname: Santelli-Rouvier
authors.forename: Vincent
authors.initials: V
authors.lastname: Papa
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Thierry
authors.initials: T
authors.lastname: Fusai
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbe
authors.forename: Daniel
authors.initials: D
authors.lastname: Parzy
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000633:toxicity*; D000962:Antimalarials / Q000633:toxicity*; D002738:Chloroquine / Q000633:toxicity*; D021261:Parasitic Sensitivity Tests / Q000379:methods; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000873:Anthracenes; D000962:Antimalarials; D002738:Chloroquine