Quinolone-3-diarylethers: A new class of antimalarial drug

Aaron Nilsen, Alexis N LaCrue, Karen Louise White, Isaac Forquer, Matthew Cross, Jutta Marfurt, Michael W Mather, Michael J Delves, David Shackleford, Fabian E Saenz, Joanne M Morrisey, Jessica Anne Steuten, Tina Mutka, Yuexin Li, Grennady Wirjanata, Eileen Ryan, Sandra Duffy, Jane Xu Kelly, Boni F Sebayang, Anne-Marie ZeemanRintis Noviyanti, Robert E Sinden, Clemens H M Kocken, Ric N Price, Vicky M Avery, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Santiago B Ferrer, Esperanza Herreros, Laura M Sanz, Francisco-Javier Gamo, Ian C Bathurst, Jeremy Burrows, Peter Siegl, R Kiplin Guy, Rolf W Winter, Akhil B Vaidya, Susan Ann Charman, Dennis E Kyle, Roman Manetsch, Michael K Risco

Research output: Contribution to journalArticleResearchpeer-review

123 Citations (Scopus)

Abstract

The goal for developing new antimalarial drugs is to find a molecule that can target multiple stages of the parasite s life cycle, thus impacting prevention, treatment, and transmission of the disease. The 4(1H)-quinolone-3- diarylethers are selective potent inhibitors of the parasite s mitochondrial cytochrome bc1 complex. These compounds are highly active against the human malaria parasites Plasmodium falciparum and Plasmodium vivax. They target both the liver and blood stages of the parasite as well as the forms that are crucial for disease transmission, that is, the gametocytes, the zygote, the ookinete, and the oocyst. Selected as a preclinical candidate, ELQ-300 has good oral bioavailability at efficacious doses in mice, is metabolically stable, and is highly active in blocking transmission in rodent models of malaria. Given its predicted low dose in patients and its predicted long half-life, ELQ-300 has potential as a new drug for the treatment, prevention, and, ultimately, eradication of human malaria.
Original languageEnglish
Pages (from-to)1 - 13
Number of pages13
JournalScience Translational Medicine
Volume5
Issue number177
DOIs
Publication statusPublished - 2013

Cite this

Nilsen, A., LaCrue, A. N., White, K. L., Forquer, I., Cross, M., Marfurt, J., ... Risco, M. K. (2013). Quinolone-3-diarylethers: A new class of antimalarial drug. Science Translational Medicine, 5(177), 1 - 13. https://doi.org/10.1126/scitranslmed.3005029