Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum

Kristen M. Massimine, Michael T. McIntosh, Lanxuan T. Doan, Chloé E. Atreya, Stephan Gromer, Worachart Sirawaraporn, David A. Elliott, Keith A. Joiner, R. Heiner Schirmer, Karen S. Anderson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

4′,5′-Dibromo-2′,7′-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits Toxoplasma gondii in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC50) of 180 μM. As a non-active-site inhibitor of the bifunctional T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on Plasmodium falciparum. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC50 of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall, our data suggest that eosin B is an effective lead compound for the development of new, more effective antimalarial drugs.

Original languageEnglish (US)
Pages (from-to)3132-3141
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume50
Issue number9
DOIs
StatePublished - Sep 1 2006

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Massimine, K. M., McIntosh, M. T., Doan, L. T., Atreya, C. E., Gromer, S., Sirawaraporn, W., Elliott, D. A., Joiner, K. A., Schirmer, R. H., & Anderson, K. S. (2006). Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrobial Agents and Chemotherapy, 50(9), 3132-3141. https://doi.org/10.1128/AAC.00621-06