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Eosin B as a Novel Antimalarial Agent for Drug-Resistant Plasmodium Falciparum

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

Antimicrob Agents Chemother. 2006 Sep;50(9):3132-41.

PMID: 16940112

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 (IC(50)) of 180 microM. 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 IC(50) 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP548243	Eosin B		548-24-3	Price

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