ArticleScience translational medicine2013
Quinolone-3-diarylethers: a new class of antimalarial drug.
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Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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128citing papers in PubMed
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Who cites it
128 citing papers in PubMed.
- Revisiting 2-Substituted-4(1Journal of medicinal chemistry · 2026Article
- Legacy 4(1ACS infectious diseases · 2026Article
- Designing novel bisquinoline antimalarials from historical 4-aminoquinolines to combat drug-resistant malaria.Antimicrobial agents and chemotherapy · 2026Article
- Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025Review
- Structure, assembly and inhibition of the Toxoplasma gondii respiratory chain supercomplex.Nature structural & molecular biology · 2025Article
- Article
- Biogenesis of CytochromesACS infectious diseases · 2025Article
- Exploration and characterization of the antimalarial activity of cyclopropyl carboxamides that target the mitochondrial protein, cytochrome b.European journal of medicinal chemistry · 2024Article
- The Combination of Buparvaquone and ELQ316 Exhibit a Stronger Effect than ELQ316 and Imidocarb AgainstPharmaceutics · 2024Article
- Biogenesis of cytochromesbioRxiv : the preprint server for biology · 2024Article
- Optimization of diastereomeric dihydropyridines as antimalarials.European journal of medicinal chemistry · 2024Article
- Article
- Incorporation of an Isohexide Subunit into the Endochin-like Quinolone Scaffold.Molecules (Basel, Switzerland) · 2024Article
- 3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.ACS infectious diseases · 2024Article
- Long-acting intramuscular injections of ELQ-331, an antimalarial agent.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2024Article
- Synthesis of Deuterated Endochin-Like Quinolones.Journal of labelled compounds & radiopharmaceuticals · 2024Article
- Unique Properties of Apicomplexan Mitochondria.Annual review of microbiology · 2023Review
- Structure of complex III with bound antimalarial agent CK-2-68 provides insights into selective inhibition of Plasmodium cytochrome bcThe Journal of biological chemistry · 2023Article
- A screen of drug-like molecules identifies chemically diverse electron transport chain inhibitors in apicomplexan parasites.PLoS pathogens · 2023Article
- Susceptibility of Ugandan Plasmodium falciparum Isolates to the Antimalarial Drug Pipeline.Microbiology spectrum · 2023Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors.
Aaron Nilsen *VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Alexis N LaCrue *Department of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA.
Karen L WhiteCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Isaac P ForquerVA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Richard M CrossDepartment of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USA.
Jutta MarfurtGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Michael W MatherDepartment of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Michael J DelvesDepartment of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
David M ShacklefordCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Fabian E SaenzDepartment of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA.
Joanne M MorriseyDepartment of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Jessica SteutenCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Tina MutkaDepartment of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA.
Yuexin LiVA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Grennady WirjanataGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Eileen RyanCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Sandra DuffyEskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, Australia.
Jane Xu KellyVA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Boni F SebayangEijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia.
Anne-Marie ZeemanDepartment of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands.
Rintis NoviyantiEijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia.
Robert E SindenDepartment of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Clemens H M KockenDepartment of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands.
Ric N PriceGlobal Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Vicky M AveryEskitis Institute for Cell & Molecular Therapies, Brisbane Innovation Park, Nathan campus, Griffith University, QLD 4111, Australia.
Iñigo Angulo-BarturenGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
María Belén Jiménez-DíazGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Santiago FerrerGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Esperanza HerrerosGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Laura M SanzGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Francisco-Javier GamoGlaxoSmithKline, Medicines Development Campus, Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Ian BathurstMedicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, Switzerland.
Jeremy N BurrowsMedicines for Malaria Venture, 20, route de Pré-Bois, PO Box 1826, 1215 Geneva 15, Switzerland.
Peter SieglSiegl Pharma Consulting LLC, Blue Bell, PA, USA.
R Kiplin GuyChemical Biology & Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678 USA.
Rolf W WinterVA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Akhil B VaidyaDepartment of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Susan A CharmanCentre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Dennis E KyleDepartment of Global Health, College of Public Health, 3720 Spectrum Blvd. (Ste 304), Tampa, FL 33612, USA.
Roman ManetschDepartment of Chemistry, University of South Florida, 4202 E. Fowler Avenue, Tampa, FL 33620-5250, USA.
Michael K RiscoeVA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.
Funding
ORGANELLE GENOMES OF MALARIAL PARASITESR01AI028398 · NIAID · MCP HAHNEMANN UNIVERSITY · PI AKHIL B VAIDYA · 1989 to 2026
$10.1MOptimizing ELQs for Treatment and Prevention of MalariaR01AI100569 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Michael Kevin RISCOE · 2014 to 2026
$8.0MAntitoxoplasmosis Drug Design and OptimizationR01AI079182 · NIAID · PORTLAND STATE UNIVERSITY · PI JONES BRANDO, LORRAINE V., RISCOE, MICHAEL KEVIN · 2009 to 2012
$1.5MDrugs targeting erythrocytic and exoerythrocytic stages of malariaR01GM097118 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI MANETSCH, ROMAN · 2011 to 2015
$1.3MDevelopment of a Chloroquine Replacement DrugRC1AI087011 · NIAID · PORTLAND STATE UNIVERSITY · PI RISCOE, MICHAEL KEVIN · 2009 to 2010
$988kOptimizing ELQs for Treatment and Prevention of MalariaR56AI100569 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI RISCOE, MICHAEL KEVIN · 2012 to 2012
$574kMitochondrial Functions in Malaria ParasitesR56AI028398 · NIAID · DREXEL UNIVERSITY · PI VAIDYA, AKHIL B · 2016 to 2016
$512kORGANELLE GENOMES OF MALARIAL PARASITESR22AI028398 · NIAID · HAHNEMANN UNIVERSITY · PI VAIDYA, AKHIL B · 1989 to 1991
–Pharmachin Optimization and TestingI01BX003312 · VA · PORTLAND VA MEDICAL CENTER · PI RISCOE, MICHAEL KEVIN · 2016 to 2025
–BLRD VA I01 BX003312NIAID NIH HHS AI079182NIAID NIH HHS AI100569NIAID NIH HHS AI28398NIAID NIH HHS R01 AI028398NIAID NIH HHS R01 AI079182NIAID NIH HHS R01 AI100569NIAID NIH HHS R56 AI100569NIAID NIH HHS RC1 AI087011NIGMS NIH HHS R01 GM097118NIGMS NIH HHS R01 GM097118-01Wellcome Trust 091625
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.
Indexed as
AnimalsAntimalarialsAtovaquoneDrug ResistanceDrug SynergismLife Cycle StagesMalariaMalaria, FalciparumMicePlasmodium falciparumPlasmodium vivaxProguanilPyridonesQuinolonesAntimalarialsAtovaquoneGW844520ProguanilPyridonesQuinolones
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