Ferroquine, an Ingenious Antimalarial Drug –Thoughts on the Mechanism of Action.docVIP

Molecules 2008, 13, 2900-2907; DOI: 10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Ferroquine, an Ingenious Antimalarial Drug –Thoughts on the Mechanism of Action Faustine Dubar 1, Jamal Khalife 2, Jacques Brocard 1, Daniel Dive 2 and Christophe Biot 1, * 1 Université des Sciences et Technologies de Lille, Unité de Catalyse et Chimie du Solide – UMR CNRS 8181, Ecole Nationale Supérieure de Chimie de Lille, Batiment C7, B.P. 90108, 59652 Villeneuve d Ascq cedex, France; E-mails: faustine.dubar@free.fr (F. D.), jacques.brocard@univ- lille1.fr (J. B.), 2 Inserm U547, Institut Pasteur, 1 rue du Pr Calmette, B.P. 245, 59019 Lille Cedex, France; E-mails: jamal.khalife@pasteur-lille.fr (J. F.), daniel.dive@pasteur-lille.fr (D. D.) * Author to whom correspondence should be addressed. E-mail: christophe.biot@ensc-lille.fr. Received: 22 October 2008; in revised form: 14 November 2008 / Accepted: 18 November 2008 / Published: 20 November 2008 Abstract: 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. Keywords: Malaria; Bioorganometallics; Ferroquine; Mechanism of action; Resistance. Introduction Malaria is a tropical disease causing almost three million deaths every year, mainly among children and pregnant women in Africa and South East Asia [1]. It is caused by single cell protozoon parasites of the Pla