Plasmodium vivax dihydrofolate reductase as a target of sulpha drugs.

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Djapa LY, Zelikson R, Delahodde A, Bolotin-Fukuhara M, Mazabraud A

Plasmodium vivax dihydrofolate reductase as a target of sulpha drugs.

FEMS Microbiol Lett. 2006 Mar;256(1):105-11.

PubMed ID

16487326 [ View in PubMed

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Abstract

Sulpha drugs act as competitive inhibitors of p-amino benzoic acid, an intermediate in the de novo folate pathway. Dihydropteroate synthase condenses sulpha drugs into sulpha-dihydropteroate (sulpha-DHP), which competes with dihydrofolate, the dihydrofolate reductase (DHFR) substrate. This designates DHFR as a possible target of sulpha-DHP. We suggest here that Plasmodium vivax DHFR is indeed the in vivo target of sulpha drugs. The wild-type DHFR expressed in Saccharomyces cerevisiae leads to cell growth inhibition, while sensitivity to the drug is exacerbated in the mutants. Contrary to what is observed with sulphanilamide, methotrexate is less effective on P. vivax-DHFR mutants than on wild-type mutant.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sulfanilamide	Dihydropteroate synthase	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details