A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds

E. Deharo, R. N. García, P. Oporto, A. Gimenez, M. Sauvain, V. Jullian, H. Ginsburg

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

56 Citas (Scopus)

Resumen

Intraerythrocytic malaria parasites produce large amounts of toxic ferriprotoporphyrin IX (FP) during their digestion of host cell haemoglobin. The inhibition of biomineralisation of FP to haemozoin (or β-haematin) by antimalarial drugs underlies their mode of action. We have developed an in vitro microassay for testing the inhibition of biomineralisation by drugs. It is based on the detection by optical density measurement of solubilised β-haematin remaining after contact with drugs. The assay uses a 192-μM haemin chloride solution in dimethyl sulfoxide, 96-well filtration microplates as well as normal microplates; it lasts 18-24h and requires a spectrophotometer. We determined by this assay the IC50 of chloroquine phosphate (28 μM) and quinine base (324 μM) and showed that unlike previous methods it is insensitive to inorganic anions. We also determined the activity of synthetic dyes and plant extract to determinate the interference of coloured compounds on the accuracy of the test. We found that methylene blue, thionine (IC50 38 and 87 μM, respectively), and an extract of plants that contains quinoline derivatives, inhibited the biomineralisation of FP regardless of their intrinsic colour.

Idioma originalInglés
Páginas (desde-hasta)252-256
Número de páginas5
PublicaciónExperimental Parasitology
Volumen100
N.º4
DOI
EstadoPublicada - 1 abr. 2002

Nota bibliográfica

Funding Information:
The project was funded by the Institut de Recherche pour le Développement (France), and the Organisacion de los Estados Americanos (OEA) proyecto Flora Regional.

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