AJTMH HINARI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am. J. Trop. Med. Hyg., 77(2), 2007, pp. 214-220
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tahar, R.
Right arrow Articles by Basco, L. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tahar, R.
Right arrow Articles by Basco, L. K.
Related Collections
Right arrow Drug-Resistance
Right arrow Malaria

Molecular Epidemiology of Malaria in Cameroon. XXV. In Vitro Activity of Fosmidomycin and its Derivatives against Fresh Clinical Isolates of Plasmodium falciparum and Sequence Analysis of 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase

Rachida Tahar AND Leonardo K. Basco*
Unité de Recherche 77 Paludologie Afro-Tropicale, Institut de Recherche pour le Développement and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon

The in vitro activities of fosmidomycin derivatives, chloroquine, and pyrimethamine were assessed by the radioisotopic assay in clinical isolates of Plasmodium falciparum. In a series of experiments with RPMI 1640 medium–10% fetal bovine serum, the geometric mean 50% inhibitory concentrations (IC50s) (n = 34) for fosmidomycin and FR900098 were 301 nM and 118 nM, respectively. In another series of experiments, the geometric mean IC50s (n = 33) for fosmidomycin and TH II46 were 413 nM and 249 nM, respectively. The IC50s were 2–3 times lower with RPMI–10% fetal bovine serum than the IC50s obtained with RPMI–10% human serum. FR900098 and TH II46 were 2.6 and 1.7 times more potent, respectively, than fosmidomycin. There was no correlation between chloroquine or pyrimethamine and fosmidomycin, which suggested the absence of in vitro cross-resistance. Sequence analysis showed five amino acid substitutions, but their possible relationship with the response to fosmidomycin is not clear. Fosmidomycin derivatives are promising candidates for further development.

Received September 3, 2006. Accepted for publication April 24, 2007.

Acknowledgments: We thank the staff of Nlongkak Catholic missionary dispensary for recruitment of patients and Dr. Jochen Wiesner (Institute of Biochemistry, University of Giessen, Giessen, Germany) for critical reading of the manuscript.

Financial support: This study was supported by the International Scientific Cooperation Project (INCO-DEV) of the European Commission (contract no. ICA4-CT-2001-10078).

* Address correspondence to Leonardo K. Basco, Unité de Recherche Paludologie Afro-Tropicale, Institut de Recherche pour le Développement et Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, BP 288, Yaoundé, Cameroon. E-mail: lkbasco{at}yahoo.fr

Authors’ addresses: Rachida Tahar and Leonardo K. Basco, Unité de Recherche Paludologie Afro-Tropicale, Institut de Recherche pour le Développement et Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, BP 288, Yaoundé, Cameroon, Telephone: 237-2223-22-32, Fax: 237-2223-00-61, E-mails: lkbasco{at}yahoo.fr and rachidatahar{at}yahoo.fr






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society of Tropical Medicine and Hygiene.