TY - JOUR
T1 - Quinolone-3-diarylethers
T2 - A new class of antimalarial drug
AU - Nilsen, Aaron
AU - LaCrue, Alexis N.
AU - White, Karen L.
AU - Forquer, Isaac P.
AU - Cross, R. Matthew
AU - Marfurt, Jutta
AU - Mather, Michael W.
AU - Delves, Michael J.
AU - Shackleford, David M.
AU - Saenz, Fabian E.
AU - Morrisey, Joanne M.
AU - Steuten, Jessica
AU - Mutka, Tina
AU - Li, Yuexin
AU - Wirjanata, Grennady
AU - Ryan, Eileen
AU - Duffy, Sandra
AU - Kelly, Jane Xu
AU - Sebayang, Boni F.
AU - Zeeman, Anne Marie
AU - Noviyanti, Rintis
AU - Sinden, Robert E.
AU - Kocken, Clemens H.M.
AU - Price, Ric N.
AU - Avery, Vicky M.
AU - Angulo-Barturen, Iñigo
AU - Jiménez-Díaz, María Belén
AU - Ferrer, Santiago
AU - Herreros, Esperanza
AU - Sanz, Laura M.
AU - Gamo, Francisco Javier
AU - Bathurst, Ian
AU - Burrows, Jeremy N.
AU - Siegl, Peter
AU - Guy, R. Kiplin
AU - Winter, Rolf W.
AU - Vaidya, Akhil B.
AU - Charman, Susan A.
AU - Kyle, Dennis E.
AU - Manetsch, Roman
AU - Riscoe, Michael K.
PY - 2013/3/20
Y1 - 2013/3/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876002292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876002292&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3005029
DO - 10.1126/scitranslmed.3005029
M3 - Article
C2 - 23515079
AN - SCOPUS:84876002292
SN - 1946-6234
VL - 5
JO - Science translational medicine
JF - Science translational medicine
IS - 177
M1 - 177ra37
ER -