Inhibitors of de novo folate enzymes in Plasmodium falciparum.

Article Details

Citation

Copy to clipboard

Nzila A

Inhibitors of de novo folate enzymes in Plasmodium falciparum.

Drug Discov Today. 2006 Oct;11(19-20):939-44. Epub 2006 Sep 7.

PubMed ID

16997145 [ View in PubMed

]

Abstract

Antifolates, inhibitors of folate synthesis or folate conversion, are used for malaria treatment. They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds compete with para-aminobenzoic acid in the active site of DHPS. The discovery of new antifolates is based on the identification of DHFR inhibitors; little work has been done on sulfur-based drugs because of their toxicity. As a result, only a few sulfur-based drugs are available. In this review, the hypothesis that compounds that compete with pteridine derivatives in active sites of de novo folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If correct, this could lead to the identification of a new family of synergizers of DHFR inhibitors.

DrugBank Data that Cites this Article

Drugs

Sulfanilamide

Drug Targets

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