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

19 Citations (Scopus)

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 2006

Fingerprint

Eosine I Bluish
Antimalarials
Plasmodium falciparum
Inhibitory Concentration 50
Toxoplasma
Cell Culture Techniques
Thioredoxin-Disulfide Reductase
Antiparasitic Agents
Intracellular Membranes
Glutathione Reductase
Folic Acid
Organelles
Oxidation-Reduction
Coloring Agents

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Massimine, K. M., McIntosh, M. T., Doan, L. T., Atreya, C. E., Gromer, S., Sirawaraporn, W., ... 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

Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. / Massimine, Kristen M.; McIntosh, Michael T.; Doan, Lanxuan T.; Atreya, Chloé E.; Gromer, Stephan; Sirawaraporn, Worachart; Elliott, David A.; Joiner, Keith A; Schirmer, R. Heiner; Anderson, Karen S.

In: Antimicrobial Agents and Chemotherapy, Vol. 50, No. 9, 09.2006, p. 3132-3141.

Research output: Contribution to journalArticle

Massimine, KM, McIntosh, MT, Doan, LT, Atreya, CE, Gromer, S, Sirawaraporn, W, Elliott, DA, Joiner, KA, Schirmer, RH & Anderson, KS 2006, 'Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum', Antimicrobial Agents and Chemotherapy, vol. 50, no. 9, pp. 3132-3141. https://doi.org/10.1128/AAC.00621-06
Massimine KM, McIntosh MT, Doan LT, Atreya CE, Gromer S, Sirawaraporn W et al. Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. Antimicrobial Agents and Chemotherapy. 2006 Sep;50(9):3132-3141. https://doi.org/10.1128/AAC.00621-06
Massimine, Kristen M. ; McIntosh, Michael T. ; Doan, Lanxuan T. ; Atreya, Chloé E. ; Gromer, Stephan ; Sirawaraporn, Worachart ; Elliott, David A. ; Joiner, Keith A ; Schirmer, R. Heiner ; Anderson, Karen S. / Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum. In: Antimicrobial Agents and Chemotherapy. 2006 ; Vol. 50, No. 9. pp. 3132-3141.
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