Journal article
Quinolone-3-diarylethers: a new class of antimalarial drug
Science translational medicine, v 5(177), pp 177ra37-177ra37
20 Mar 2013
PMID: 23515079
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Quinolone-3-diarylethers: a new class of antimalarial drug
- Creators
- Aaron Nilsen - VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USAAlexis N LaCrue - Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USAKaren L White - Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaIsaac P Forquer - VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USARichard M Cross - Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USAJutta Marfurt - Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, AustraliaMichael W Mather - Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAMichael J Delves - Department of Life Sciences, Imperial College London, London SW7 2AZ, United KingdomDavid M Shackleford - Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaFabian E Saenz - Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USAJoanne M Morrisey - Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAJessica Steuten - Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaTina Mutka - Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USAYuexin Li - VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USAGrennady Wirjanata - Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, AustraliaEileen Ryan - Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaSandra Duffy - Eskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, AustraliaJane Xu Kelly - VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USABoni F Sebayang - Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, IndonesiaAnne-Marie Zeeman - Department of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The NetherlandsRintis Noviyanti - Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, IndonesiaRobert E Sinden - Department of Life Sciences, Imperial College London, London SW7 2AZ, United KingdomClemens H M Kocken - Department of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The NetherlandsRic N Price - Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, UKVicky M Avery - Eskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, AustraliaIñigo Angulo-Barturen - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainMaría Belén Jiménez-Díaz - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainSantiago Ferrer - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainEsperanza Herreros - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainLaura M Sanz - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainFrancisco-Javier Gamo - GlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, SpainIan Bathurst - Medicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, SwitzerlandJeremy N Burrows - Medicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, SwitzerlandPeter Siegl - Siegl Pharma Consulting LLC, Blue Bell, PA, USAR Kiplin Guy - Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678 USARolf W Winter - VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USAAkhil B Vaidya - Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USASusan A Charman - Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaDennis E Kyle - Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USARoman Manetsch - Department of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USAMichael K Riscoe - Department of Molecular Microbiology and Immunology, 3181 Sam Jackson Blvd., Portland, Oregon 97239, USA
- Publication Details
- Science translational medicine, v 5(177), pp 177ra37-177ra37
- Publisher
- American Association for the Advancement of Science (AAAS); United States
- Grant note
- AI100569 / NIAID NIH HHS R56 AI100569 / NIAID NIH HHS AI079182 / NIAID NIH HHS R01 AI079182 / NIAID NIH HHS R01 AI100569 / NIAID NIH HHS 091625 / Wellcome Trust R01 GM097118-01 / NIGMS NIH HHS R01 AI028398 / NIAID NIH HHS RC1 AI087011 / NIAID NIH HHS R01 GM097118 / NIGMS NIH HHS I01 BX003312 / BLRD VA AI28398 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000316454100006
- Scopus ID
- 2-s2.0-84876002292
- Other Identifier
- 991014877822304721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology
- Medicine, Research & Experimental