Probing the Role of the Covalent Linkage of Ferrocene into a Chloroquine Template

• Published in: Journal of medicinal chemistry Vol. 49; no. 15; pp. 4707 - 4714
• Main Authors: Biot, Christophe, Daher, Wassim, Ndiaye, Cheikh M, Melnyk, Patricia, Pradines, Bruno, Chavain, Natascha, Pellet, Alain, Fraisse, Laurent, Pelinski, Lydie, Jarry, Christian, Brocard, Jacques, Khalife, Jamal, Forfar-Bares, Isabelle, Dive, Daniel
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.07.2006; Amer Chemical Soc
• Subjects: Aminoquinolines; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; Biological and medical sciences; Chemical Sciences; Chemistry, Medicinal; Chloroquine - chemistry; Ferrous Compounds - chemical synthesis; Ferrous Compounds - chemistry; Ferrous Compounds - pharmacology; Hemeproteins - antagonists & inhibitors; Hemeproteins - chemical synthesis; Life Sciences; Life Sciences & Biomedicine; Medical sciences; Medicinal Chemistry; Microbiology and Parasitology; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Science & Technology; Structure-Activity Relationship; PHYSICOCHEMICAL PROPERTIES; ANTIPLASMODIAL ACTIVITY; FERROCHLOROQUINE; METABOLITES; CYANOHYDRIDOBORATE; ANALOGS; ANTIMALARIAL ACTIVITY; ACTIVITY IN-VITRO; FERROQUINE; Protozoa; Antimalarial; Apicomplexa; Chloroquine; Quinoline derivatives; In vitro; Metallocene; Antiprotozoal agent; Iron Organic compounds; Plasmodium falciparum; Structure activity relation; Covalent bond; Pigments; Parasiticide; Property structure relationship; Mechanism of action; Chemical synthesis; Lipophilicity; Physicochemical properties
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060259d

A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the β-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.