Enhancement of the antimalarial activity of ciprofloxacin using a double prodrug/bioorganometallic approach.
The derivatization of the fluoroquinolone ciprofloxacin greatly increases its antimalarial activity by combining bioorganometallic chemistry and the prodrug approach. Two new achiral compounds 2 and 4 were found to be 10- to 100-fold more active than ciprofloxacin against Plasmodium falciparum chloroquine-susceptible and chloroquine-resistant strains. These achiral derivatives killed parasites more rapidly than did ciprofloxacin. Compounds 2 and 4 were revealed to be promising leads, creating a new family of antimalarial agents.
Dubar
Faustine
F
Universite de Lille 1, CNRS UMR 8181, ENSCL,Villeneuve d'Ascq Cedex, France.
Anquetin
Guillaume
G
Pradines
Bruno
B
Dive
Daniel
D
Khalife
Jamal
J
Biot
Christophe
C
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology*; D000075163:Metallocenes; D010963:Plasmodium falciparum / Q000187:drug effects; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*
D000634:Aminoquinolines; D000962:Antimalarials; D005296:Ferrous Compounds; D000075163:Metallocenes; D011355:Prodrugs; D002939:Ciprofloxacin; C479230:ferroquine; C004998:ferrocene