Titre du document / Document title

In vitro activity of iron-binding compounds against Senegalese isolates of Plasmodium falciparum

Auteur(s) / Author(s)

PRADINES B. ^{(1 2)} ; TALL A. ⁽³⁾ ; RAMIANDRASOA F. ⁽⁴⁾ ; SPIEGEL A. ^{(3 5)} ; SOKHNA C. ⁽⁶⁾ ; FUSAI T. ^{(1 2)} ; MOSNIER J. ^{(1 2)} ; DARIES W. ^{(1 2)} ; TRAPE J. F. ⁽⁶⁾ ; KUNESCH G. ⁽⁴⁾ ; PARZY D. ^{(2 7)} ; ROGIER C. ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Le Pharo, 13998 Marseille, FRANCE
⁽²⁾ Institut Fédératif de la Recherche no 48, 13385 Marseille, FRANCE
⁽³⁾ Service d'Epidémiologie, Institut Pasteur, Dakar, SENEGAL
⁽⁴⁾ Laboratoire de Chimie Bioorganique et Bioinorganique, CNRS URA 1384, Institut de Chimie Moléculaire d'Orsay, 91405 Orsay, FRANCE
⁽⁵⁾ Département d'Epidémiologie et de Santé Publique, Ecole d'Application du Service de Santé des Armées, 94998 Saint Mandé, FRANCE
⁽⁶⁾ UR 077 de Paludologie Afrotropicale, Institut pour la Recherche et le Développement, Dakar, SENEGAL
⁽⁷⁾ Unité de Recherche en Physiopathologie et de Pharmacogénétique Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Le Pharo, 13998 Marseille, FRANCE

Résumé / Abstract

Objectives: The in vitro activities of FR160, a synthetic catecholate siderophore, and two iron-binding agents, desferrioxamine and doxycycline, were evaluated against Plasmodium falciparum isolates. Correlations between these compounds and standard antimalarial drugs (chioroquine, quinine, amodiaquine, pyronaridine, artemether, artesunate, atovaquone, cycloguanil and pyrimethamine) were assessed to determine any degree of cross-resistance. Methods: Between October 1997 and February 1998, and September and November 1998,189 P. falciparum isolates were obtained in Dielmo and Ndiop (Dakar). Their susceptibilities were assessed using an isotopic, microwell format, drug susceptibility test. Results: The 137 inhibitory concentrations (IC₅₀) values of FR160 ranged from 0.1 to 10 μM and the geometric mean IC₅₀ was 1.48 μM (95% Cl = 1.29-1.68 μM). The geometric mean IC₅₀ of doxycycline for 121 isolates was 18.9 μM (95% Cl = 16.8-21.3 μM) and that of desferrioxamine for 73 isolates was 20.7 μM (95% Cl = 17.3-24.8 μM). FR160 was significantly less active against the chloroquine-resistant isolates (P < 0.0001). The mean IC₅₀s of doxycycline were significantly higher for the chloroquine-susceptible isolates than for the resistant parasites (P= 0.0447). There was a weak correlation between the responses to FR160, desferrioxamine or doxycycline and those to the other antimalarial compounds (r2 < 0.22). Conclusions: The activities of FR160 and desferrioxamine, determined for P. falciparum clones, were confirmed against 137 isolates. The coefficients of determination between the responses to FR160, doxycycline or desferrioxamine and those to all the antimalarial drugs tested are too weak to suggest cross-resistance. FR160 could be a rationale partner to use in combination with doxycycline.

Revue / Journal Title

Journal of antimicrobial chemotherapy   ISSN 0305-7453   CODEN JACHDX 

Source / Source

2006, vol. 57, n^o6, pp. 1093-1099 [7 page(s) (article)] (63 ref.)

Langue / Language

Anglais

Editeur / Publisher

Oxford University Press, Oxford, ROYAUME-UNI  (1975) (Revue)

Mots-clés anglais / English Keywords

Infection ; Parasitosis ; Protozoal disease ; Protozoa ; Apicomplexa ; Africa ; Drug ; Parasiticide ; Antimalarial ; Treatment ; Chemotherapy ; Chelating agent ; Malaria ; Plasmodium falciparum ; Isolate ; Senegal ; Iron ; Biological activity ; In vitro ;

Mots-clés français / French Keywords

Infection ; Parasitose ; Protozoose ; Protozoa ; Apicomplexa ; Afrique ; Médicament ; Antiparasitaire ; Antipaludique ; Traitement ; Chimiothérapie ; Chélateur ; Paludisme ; Plasmodium falciparum ; Isolat ; Sénégal ; Fer ; Activité biologique ; In vitro ;

Mots-clés espagnols / Spanish Keywords

Infección ; Parasitosis ; Protozoosis ; Protozoa ; Apicomplexa ; Africa ; Medicamento ; Antiparasitario ; Antipalúdico ; Tratamiento ; Quimioterapia ; Quelante ; Paludismo ; Plasmodium falciparum ; Aislado ; Senegal ; Hierro ; Actividad biológica ; In vitro ;

Mots-clés d'auteur / Author Keywords

malaria ; iron chelation ; chemotherapy ; antimalarial drugs ; Senegal ;

Localisation / Location

INIST-CNRS, Cote INIST : 17084, 35400014249016.0110