Ferroquine, an ingenious antimalarial drug: thoughts on the mechanism of action.
Ferroquine (FQ or SR97193) is a novel antimalarial drug candidate, currently in development at Sanofi-Aventis. In contrast to conventional drugs, FQ is the first organometallic drug: a ferrocenyl group covalently flanked by a 4-aminoquinoline and a basic alkylamine. FQ is able to overcome the CQ resistance problem, an important limit to the control of Plasmodium falciparum, the principal causative agent of malaria. After fifteen years of effort, it is now possible to propose a multifactorial mechanism of action of FQ by its capacity to target lipids, to inhibit the formation of hemozoin and to generate reactive oxygen species.
Dubar
Faustine
F
Université des Sciences et Technologies de Lille, Unité de Catalyse et Chimie du Solide, UMR CNRS 8181, Ecole Nationale Supérieure de Chimie de Lille, Bâtiment C7, Villeneuve d'Ascq Cedex, France. faustine.dubar@free.fr
Khalife
Jamal
J
Brocard
Jacques
J
Dive
Daniel
D
Biot
Christophe
C
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D004351:Drug Resistance; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D006427:Hemin / Q000037:antagonists & inhibitors; D008055:Lipids / Q000737:chemistry; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000138:chemical synthesis
D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D008055:Lipids; D000075163:Metallocenes; D017382:Reactive Oxygen Species; D006427:Hemin; C479230:ferroquine