Probing the role of the covalent linkage of ferrocene into a chloroquine template.
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 beta-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.
Biot
Christophe
C
Unité de Catalyse et Chimie du Solide - UMR CNRS 8181, ENSCL, Bâtiment C7, USTL, B.P. 90108, 59652, Villeneuve d' Ascq Cedex, France. christophe.biot@ensc-lille.fr
Daher
Wassim
W
Ndiaye
Cheikh M
CM
Melnyk
Patricia
P
Pradines
Bruno
B
Chavain
Natascha
N
Pellet
Alain
A
Fraisse
Laurent
L
Pelinski
Lydie
L
Jarry
Christian
C
Brocard
Jacques
J
Khalife
Jamal
J
Forfar-Bares
Isabelle
I
Dive
Daniel
D
D000634:Aminoquinolines; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002738:Chloroquine / Q000737:chemistry*; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000138:chemical synthesis; D000075163:Metallocenes; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D006420:Hemeproteins; D000075163:Metallocenes; D011804:Quinolines; C020753:hemozoin; D002738:Chloroquine; C479230:ferroquine