ArticleThe American journal of tropical medicine and hygiene2015
Inhibition of cytochrome bc1 as a strategy for single-dose, multi-stage antimalarial therapy.
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Article in The American journal of tropical medicine and hygiene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
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- Chemoprevention of malaria with long-acting oral and injectable drugs: an updated target product profile.Malaria journal · 2024Review
- 3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.ACS infectious diseases · 2024Article
- Synthesis of Deuterated Endochin-Like Quinolones.Journal of labelled compounds & radiopharmaceuticals · 2024Article
- Identification of complex III, NQR, and SDH as primary bioenergetic enzymes during the stationary phase ofFrontiers in microbiology · 2024Article
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- Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.Frontiers in cellular and infection microbiology · 2022Review
- Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.International journal for parasitology. Drugs and drug resistance · 2021Article
- Treatment of Human Babesiosis: Then and Now.Pathogens (Basel, Switzerland) · 2021Review
- A New Scalable Synthesis of ELQ-300, ELQ-316, and other Antiparasitic Quinolones.Organic process research & development · 2021Article
- Effective Therapy Targeting CytochromeAntimicrobial agents and chemotherapy · 2021Article
- PfMFR3: A Multidrug-Resistant Modulator inACS infectious diseases · 2021Article
- Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites.Scientific reports · 2021Article
- Novel Endochin-Like Quinolones Exhibit PotentAntimicrobial agents and chemotherapy · 2020Article
- Probing the Open Global Health Chemical Diversity Library for Multistage-Active Starting Points for Next-Generation Antimalarials.ACS infectious diseases · 2020Article
- Antimalarial Agents as Therapeutic Tools Against Toxoplasmosis-A Short Bridge between Two Distant Illnesses.Molecules (Basel, Switzerland) · 2020Review
- Discovery and Structural Optimization of Acridones as Broad-Spectrum Antimalarials.Journal of medicinal chemistry · 2019Article
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Authors and funding
17 authors at 1 institution in 1 country.
Allison M SticklesDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Li-Min TingDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Joanne M MorriseyDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Yuexin LiDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Michael W MatherDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Erin MeermeierDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
April M PershingDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Isaac P ForquerDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Galen P MileyDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Sovitj PouDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Rolf W WinterDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
David J HinrichsDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Jane X KellyDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Kami KimDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Akhil B VaidyaDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon.
Michael K RiscoeDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon nilsena@ohsu.edu riscoem@ohsu.edu.
Aaron NilsenDepartments of Physiology and Pharmacology, Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon; Departments of Medicine, Pathology, and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania; VA Medical Center, Portland, Oregon nilsena@ohsu.edu riscoem@ohsu.edu.
Oregon Health & Science University · US
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
$8.0MProgram in Molecular and Cellular BiosciencesT32GM071338 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI MASLEN, CHERYL L · 2005 to 2020
$3.5MAntitoxoplasmosis Drug Design and OptimizationR01AI079182 · NIAID · PORTLAND STATE UNIVERSITY · PI JONES BRANDO, LORRAINE V., RISCOE, MICHAEL KEVIN · 2009 to 2012
$1.5MOptimizing 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
$512kIVIS Spectrum imager of bioluminescence and fluorescenceS10RR027308 · NCRR · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI KIM, KAMI · 2010 to 2010
$360kORGANELLE 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
–NCRR NIH HHS S10 RR027308NCRR NIH HHS S10RR027308NIAID NIH HHS AI028398NIAID NIH HHS AI079182NIAID NIH HHS AI100569NIAID NIH HHS R01 AI028398NIAID NIH HHS R01 AI079182NIAID NIH HHS R01 AI100569NIAID NIH HHS R56 AI028398NIAID NIH HHS R56 AI100569
Abstract
Single-dose therapies for malaria have been proposed as a way to reduce the cost and increase the effectiveness of antimalarial treatment. However, no compound to date has shown single-dose activity against both the blood-stage Plasmodium parasites that cause disease and the liver-stage parasites that initiate malaria infection. Here, we describe a subset of cytochrome bc1 (cyt bc1) inhibitors, including the novel 4(1H)-quinolone ELQ-400, with single-dose activity against liver, blood, and transmission-stage parasites in mouse models of malaria. Although cyt bc1 inhibitors are generally classified as slow-onset antimalarials, we found that a single dose of ELQ-400 rapidly induced stasis in blood-stage parasites, which was associated with a rapid reduction in parasitemia in vivo. ELQ-400 also exhibited a low propensity for drug resistance and was active against atovaquone-resistant P. falciparum strains with point mutations in cyt bc1. Ultimately, ELQ-400 shows that cyt bc1 inhibitors can function as single-dose, blood-stage antimalarials and is the first compound to provide combined treatment, prophylaxis, and transmission blocking activity for malaria after a single oral administration. This remarkable multi-stage efficacy suggests that metabolic therapies, including cyt bc1 inhibitors, may be valuable additions to the collection of single-dose antimalarials in current development.
Indexed as
AnimalsAntimalarialsDrug ResistanceElectron Transport Complex IIIFemaleMalaria, FalciparumMiceParasitemiaPhenyl EthersPlasmodium falciparumPlasmodium yoeliiQuinolonesAntimalarialsElectron Transport Complex IIIELQ-400Phenyl EthersQuinolones
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.