ArticleScientific reports2017
Griseofulvin impairs intraerythrocytic growth of Plasmodium falciparum through ferrochelatase inhibition but lacks activity in an experimental human infection study.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 221 citations in OpenAlex.
- Thermo-Structural Characterization of Phase Transitions in Amorphous Griseofulvin: From Sub-TMolecules (Basel, Switzerland) · 2024Article
- Long-Acting Microparticle Formulation of Griseofulvin for Ocular Neovascularization Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Review
- Malaria parasite heme biosynthesis promotes and griseofulvin protects against cerebral malaria in mice.Nature communications · 2022Article
- Heme is involved in the exogenous ALA-promoted growth and antioxidant defense system of cucumber seedlings under salt stress.BMC plant biology · 2022Article
- Small-molecule inhibitors of ferrochelatase are antiangiogenic agents.Cell chemical biology · 2022Article
- Haematological response in experimental human Plasmodium falciparum and Plasmodium vivax malaria.Malaria journal · 2021Article
- Pipecolisporin, a Novel Cyclic Peptide with Antimalarial and Antitrypanosome Activities from a Wheat EndophyticPharmaceuticals (Basel, Switzerland) · 2021Article
- Multipurpose Drugs Active Against BothFrontiers in cellular and infection microbiology · 2021Review
- Ferrochelatase regulates retinal neovascularization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Article
- Host Porphobilinogen Deaminase Deficiency Confers Malaria Resistance inFrontiers in cellular and infection microbiology · 2020Article
- Controlled Human Malaria Infection: Applications, Advances, and Challenges.Infection and immunity · 2018Review
- Plasmodium heme biosynthesis: To be or not to be essential?PLoS pathogens · 2017Review
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6 authors at 4 institutions in 1 country.
Funding
Abstract
Griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome P450-mediated production of N-methyl protoporphyrin IX (N-MPP). N-MPP is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage Plasmodium falciparum. Novel drugs against Plasmodium are needed to achieve malaria elimination. Thus, we investigated whether griseofulvin shows anti-plasmodial activity. We observed that the intraerythrocytic growth of P. falciparum is inhibited in red blood cells pretreated with griseofulvin in vitro. Treatment with 100 μM griseofulvin was sufficient to prevent parasite growth and induce the production of N-MPP. Inclusion of the ferrochelatase substrate PPIX blocked the inhibitory activity of griseofulvin, suggesting that griseofulvin exerts its activity through the N-MPP-dependent inhibition of ferrochelatase. In an ex-vivo study, red blood cells from griseofulvin-treated subjects were refractory to the growth of cultured P. falciparum. However, in a clinical trial griseofulvin failed to show either therapeutic or prophylactic effect in subjects infected with blood stage P. falciparum. Although the development of griseofulvin as an antimalarial is not warranted, it represents a novel inhibitor of P. falciparum growth and acts via the N-MPP-dependent inhibition of ferrochelatase.
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