ArticleParasitology research2008
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.
Article in Parasitology research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Effects and safety of periconceptional oral folate supplementation for preventing birth defects.The Cochrane database of systematic reviews · 2015Pooled it
- Effects and safety of periconceptional folate supplementation for preventing birth defects.The Cochrane database of systematic reviews · 2010Pooled it
- A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers.Malaria journal · 2011Trial
- Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) amino acid 1466 associated with resistance to sulfadoxine-pyrimethamine treatment.Antimicrobial agents and chemotherapy · 2009Trial
- Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum.Nature communications · 2026Article
- Improved methyl supply for 5-methyltetrahydrofolate production in E. coli through a novel C1 transfer pathway.Microbial cell factories · 2025Article
- Potential selection of antimony and methotrexate cross-resistance in Leishmania infantum circulating strains.PLoS neglected tropical diseases · 2024Article
- Effect of immunosuppressants on the parasite load developed in, and immune response to, visceral leishmaniasis: A comparative study in a mouse model.PLoS neglected tropical diseases · 2021Article
- Engineering of Biosynthesis Pathway and NADPH Supply for Improved L-5-Methyltetrahydrofolate Production byJournal of microbiology and biotechnology · 2019Article
- Safety and benefits of interventions to increase folate status in malaria-endemic areas.British journal of haematology · 2017Review
- The molecular basis of antifolate resistance in Plasmodium falciparum: looking beyond point mutations.Annals of the New York Academy of Sciences · 2015Review
- The molecular basis of folate salvage in Plasmodium falciparum: characterization of two folate transporters.The Journal of biological chemistry · 2011Article
- Scaling up of intermittent preventive treatment of malaria in pregnancy using sulphadoxine-pyrimethamine: prospects and challenges.Maternal and child health journal · 2011Article
- Vivax malaria: old drug, new uses?The Journal of infectious diseases · 2011Article
- Characterisation of the bifunctional dihydrofolate synthase-folylpolyglutamate synthase from Plasmodium falciparum; a potential novel target for antimalarial antifolate inhibition.Molecular and biochemical parasitology · 2010Article
- Effects of in vitro exposure of Echinococcus multilocularis metacestodes to cytostatic drugs on in vivo growth and proliferation of the parasite.Parasitology research · 2010Article
- Preclinical evaluation of the antifolate QN254, 5-chloro- N'6'-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate.Antimicrobial agents and chemotherapy · 2010Article
- Anticancer agents against malaria: time to revisit?Trends in parasitology · 2010Article
- A pre-emptive strike against malaria's stealthy hepatic forms.Nature reviews. Drug discovery · 2009Review
- In vitro activity of antifolate and polymorphism in dihydrofolate reductase of Plasmodium falciparum isolates from the Kenyan coast: emergence of parasites with Ile-164-Leu mutation.Antimicrobial agents and chemotherapy · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The folate derivatives folic acid (FA) and folinic acid (FNA) decrease the in vivo and in vitro activities of antifolate drugs in Plasmodium falciparum. However, the effects of 5-methyl-tetrahydrofolate (5-Me-THF) and tetrahydrofolate (THF), the two dominant circulating folate forms in humans, have not been explored yet. We have investigated the effects of FA, FNA, 5-Me-THF, and THF on the in vitro activity of the antimalarial antifolates pyrimethamine and chlorcycloguanil and the anticancer antifolates methotrexate (MTX), aminopterin, and trimetrexate (TMX), against P. falciparum. The results indicate that these anticancers are potent against P. falciparum, with IC50 < 50 nM. 5-Me-THF does not significantly decrease the activity of all tested drugs, and none of the tested folate derivatives significantly decrease the activity of these anticancers. Thus, malaria folate metabolism has features different from those in human, and the exploitation of this difference could lead to the discovery of new drugs to treat malaria. For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.