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Djapa L. Y., Basco Leonardo, Zelikson R., Rosowsky A., Djaman J. A., Yonkeu J. N., Bolotin Fukuhara M., Mazabraud A. Antifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum. Molecular and Biochemical Parasitology, 2007, 156 (1), p. 89-92. ISSN 0166-6851

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Lien direct chez l'éditeur doi:10.1016/j.molbiopara.2007.07.009

TitreAntifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum
Année de publication2007
Type de documentArticle référencé dans le Web of Science : 000250399200011
AuteursDjapa L. Y., Basco Leonardo, Zelikson R., Rosowsky A., Djaman J. A., Yonkeu J. N., Bolotin Fukuhara M., Mazabraud A.
SourceMolecular and Biochemical Parasitology, 2007, 156 (1), p. 89-92. ISSN 0166-6851
RésuméThe presence of homologous point mutations in the dhfr gene in Plasmodium vivax and Plasmodium falciparum is associated with resistance to antifolate drugs. The spread of antifolate resistance encouraged research for novel antifolate drugs active against both wild-type and dhfr-mutant strains of malaria parasites. Because P. vivax cannot be easily maintained in culture, we transformed a Saccharomyces cerevisiae DHFR-deleted mutant to express wild-type P. vivax dhfr gene and its mutant forms. Twenty-five dicyclic and tricyclic 2,4-diaminopyrimidine derivatives were screened. Six quinazoline compounds showed selective inhibition of yeast transformants expressing R vivax dhfr genes. The 50% inhibitory concentration (IC50) of these six compounds was determined against field isolates of P falciparum. Our results suggest that a close relationship between the yeast assay based on expression of R vivax dhfr genes and the in vitro test using P falciparum parasites in culture is a promising initial step for drug screening.
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