| Literature DB >> 23515079 |
Aaron Nilsen1, Alexis N LaCrue2, Karen L White3, Isaac P Forquer1, Richard M Cross4, Jutta Marfurt5, Michael W Mather6, Michael J Delves7, David M Shackleford3, Fabian E Saenz2, Joanne M Morrisey6, Jessica Steuten3, Tina Mutka2, Yuexin Li1, Grennady Wirjanata5, Eileen Ryan3, Sandra Duffy8, Jane Xu Kelly1, Boni F Sebayang9, Anne-Marie Zeeman10, Rintis Noviyanti9, Robert E Sinden7, Clemens H M Kocken10, Ric N Price5,11, Vicky M Avery8, Iñigo Angulo-Barturen12, María Belén Jiménez-Díaz12, Santiago Ferrer12, Esperanza Herreros12, Laura M Sanz12, Francisco-Javier Gamo12, Ian Bathurst13, Jeremy N Burrows13, Peter Siegl14, R Kiplin Guy15, Rolf W Winter1, Akhil B Vaidya6, Susan A Charman3, Dennis E Kyle2, Roman Manetsch4, Michael K Riscoe1,16.
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.Entities:
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Year: 2013 PMID： 23515079 PMCID： PMC4227885 DOI： 10.1126/scitranslmed.3005029
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956