Quinolone-3-diarylethers: a new class of antimalarial drug.

Autor: Nilsen A; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA., LaCrue AN; Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA., White KL; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia., Forquer IP; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA., Cross RM; Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USA., Marfurt J; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia., Mather MW; Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA., Delves MJ; Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom., Shackleford DM; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia., Saenz FE; Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA., Morrisey JM; Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA., Steuten J; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia., Mutka T; Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA., Li Y; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA., Wirjanata G; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia., Ryan E; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia., Duffy S; Eskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, Australia., Kelly JX; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA., Sebayang BF; Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia., Zeeman AM; Department of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands., Noviyanti R; Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia., Sinden RE; Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom., Kocken CHM; Department of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands., Price RN; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, UK., Avery VM; Eskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, Australia., Angulo-Barturen I; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Jiménez-Díaz MB; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Ferrer S; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Herreros E; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Sanz LM; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Gamo FJ; GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain., Bathurst I; Medicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, Switzerland., Burrows JN; Medicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, Switzerland., Siegl P; Siegl Pharma Consulting LLC, Blue Bell, PA, USA., Guy RK; Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678 USA., Winter RW; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA., Vaidya AB; Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA., Charman SA; Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia., Kyle DE; Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA., Manetsch R; Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USA., Riscoe MK; VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.; Department of Molecular Microbiology and Immunology, 3181 Sam Jackson Blvd., Portland, Oregon 97239, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2013 Mar 20; Vol. 5 (177), pp. 177ra37.
DOI: 10.1126/scitranslmed.3005029
Abstrakt: 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.
Databáze: MEDLINE