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Assessment of Plasmodium falciparum resistance to ferroquine (SSR97193) in field isolates and in W2 strain under pressure
- Source :
- Malaria Journal, Malaria Journal, BioMed Central, 2006, 5, pp.11. ⟨10.1186/1475-2875-5-11⟩, Malaria Journal, 2006, 5, pp.11. ⟨10.1186/1475-2875-5-11⟩, Malaria Journal (5), 1-8. (2006), Malaria Journal, Vol 5, Iss 1, p 11 (2006)
- Publication Year :
- 2006
- Publisher :
- HAL CCSD, 2006.
-
Abstract
- Background Ferroquine (FQ), or SSR97193, is a novel antimalarial drug currently in phase I clinical trials. FQ is a unique organometallic compound designed to overcome the chloroquine (CQ) resistance problem. FQ revealed to be equally active on CQ-sensitive and CQ-resistant Plasmodium falciparum laboratory strains and field isolates. FQ is also curative on rodent malaria parasites. As FQ will be tested in patients, the potential for resistance to this drug was evaluated. Methods The relationship between CQ-resistant transporter gene genotype and susceptibility to FQ were studied in 33 Cambodian P. falciparum field isolates previously studied for their in vitro response to CQ. In parallel, the ability of the CQ-resistant strain W2, to become resistant to FQ under drug pressure was assessed. Results The IC50 values for FQ in field isolates were found to be unrelated to mutations occurring in the P. falciparum chloroquine resistance transporter (PfCRT) or to the level of expression of the corresponding mRNA. In vitro, under a drug pressure of 100 nM of FQ, transient survival was observed in only one of two experiments. Conclusion Field isolates studies and experimental drug pressure experiments showed that FQ overcomes CQ resistance, which reinforces the potential of this compound as a new antimalarial drug.
- Subjects :
- Metallocenes
Drug Resistance
Protozoan Proteins
Drug resistance
Pharmacology
Parasitic Sensitivity Tests
Chloroquine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Genotype
Cells, Cultured
media_common
0303 health sciences
Membrane transport protein
Flow Cytometry
3. Good health
Infectious Diseases
Aminoquinolines
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
SDV:MHEP:MI
medicine.drug
Drug
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
media_common.quotation_subject
Plasmodium falciparum
Biology
lcsh:Infectious and parasitic diseases
Antimalarials
Inhibitory Concentration 50
03 medical and health sciences
medicine
Animals
lcsh:RC109-216
Amino Acid Sequence
Ferrous Compounds
030304 developmental biology
Blood Cells
030306 microbiology
Research
Genetic Variation
Membrane Transport Proteins
biology.organism_classification
medicine.disease
Virology
Parasitology
biology.protein
Malaria
Subjects
Details
- Language :
- English
- ISSN :
- 14752875
- Database :
- OpenAIRE
- Journal :
- Malaria Journal, Malaria Journal, BioMed Central, 2006, 5, pp.11. ⟨10.1186/1475-2875-5-11⟩, Malaria Journal, 2006, 5, pp.11. ⟨10.1186/1475-2875-5-11⟩, Malaria Journal (5), 1-8. (2006), Malaria Journal, Vol 5, Iss 1, p 11 (2006)
- Accession number :
- edsair.doi.dedup.....ca720f834b930be00fddf2a3be1a0deb