Enhancement of the antimalarial activity of ciprofloxacin using a double prodrug/bioorganometallic approach

Faustine Dubar (1) , G. Anquetin (1, 2) , Bruno Pradines (3) , Daniel Dive (4) , Jamal Khalife (4) , Christophe Biot (1, 5)

1 UCCS - Unité de Catalyse et Chimie du Solide - UMR 8181
2 ITODYS (UMR_7086) - Interfaces, Traitements, Organisation et Dynamique des Systèmes
3 Unité de Recherche en Biologie et Epidémiologie Parasitaires
4 Schistosomiase, paludisme et inflammation
5 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576

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 chloroquinesusceptible 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.

Domaines: Biochimie [q-bio.BM]

Faustine Dubar, G. Anquetin, Bruno Pradines, Daniel Dive, Jamal Khalife, et al.. Enhancement of the antimalarial activity of ciprofloxacin using a double prodrug/bioorganometallic approach. Journal of Medicinal Chemistry, 2009, 52 (24), pp.7954-7957. ⟨10.1021/jm901357n⟩. ⟨hal-00641967⟩