Evidence map›Paper›PMID 41980931›Full record

ArticleNature communications2026

Potent acridone antimalarial against all three life stages of Plasmodium.

Papireddy Kancharla, Rozalia A Dodean, Yuexin Li, Xiaowei Zhang, Sean Kelly, Jordan Charlton, Angely J Binauhan, Kimberly Navarrete, Laurize Garcia, Jianbing Mu and 48 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Evaluating acridones as novel therapeutics for human babesiosis.Antimicrobial agents and chemotherapy · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

58 authors.

Papireddy KancharlaDepartment of Chemistry, Portland State University, Portland, OR, USA. papiredd@pdx.edu.ORCID 0000-0002-6381-1236
Rozalia A DodeanDepartment of Chemistry, Portland State University, Portland, OR, USA.
Yuexin LiDepartment of Veterans Affairs Medical Center, Portland, OR, USA.
Xiaowei ZhangDepartment of Veterans Affairs Medical Center, Portland, OR, USA.
Sean KellyDepartment of Veterans Affairs Medical Center, Portland, OR, USA.
Jordan CharltonDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.
Angely J BinauhanDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.
Kimberly NavarreteDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.ORCID 0009-0001-6375-5019
Laurize GarciaDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.
Jianbing MuLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA.ORCID 0000-0001-6012-8389
Jinghua LuLab of Immunogenetics, Structural Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Diana CaridhaExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Michael S MadejczykExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Xiannu JinExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
William E DennisExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Karl KudybaExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Sharon McEnearneyExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Patricia J LeeExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Cameron BlountExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Jesse DeLucaExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Chau VuongExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Kristina PannoneExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Hieu T DinhExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Kennedy MdakiExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Susan LeedExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Monica L MartinExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Brandon S PybusExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Geoffrey C ChinExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.ORCID 0009-0001-6793-3337
Anongruk Chim-OngDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Liwang CuiDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.ORCID 0000-0002-8338-1974
Tarrick QahashEck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dam, IN, USA.
Douglas A ShoueEck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dam, IN, USA.
Michael T FerdigEck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dam, IN, USA.ORCID 0000-0003-3516-9829
Frank P MockenhauptInstitute of International Health, Charité Center for Global Health, Charité-Universitaetsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Welmoed van LoonInstitute of International Health, Charité Center for Global Health, Charité-Universitaetsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID 0000-0003-3331-3997
Jules M NdoliCollege of Medicine and Health Sciences, University Teaching Hospital of Butare, University of Rwanda, Huye, Rwanda.
Heather KudybaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA.
Joel Vega-RodriguezLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA.ORCID 0000-0002-9576-0058
Martin OkitwiInfectious Diseases Research Collaboration, Kampala, Uganda.ORCID 0000-0003-2712-2174
Oriana KreutzfeldDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Cristina DocanBiosciences Division, SRI International, Menlo Park, CA, USA.
Carol GreenBiosciences Division, SRI International, Menlo Park, CA, USA.
Ying LiuBiosciences Division, SRI International, Menlo Park, CA, USA.
Aaron AgulayBiosciences Division, SRI International, Menlo Park, CA, USA.
Jon MirsalisBiosciences Division, SRI International, Menlo Park, CA, USA.
Sarah N FarrellSchool of Biosciences, The University of Melbourne, Parkville, VIC, Australia.
Alexandra S ProbstDepartment of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.
Aaron NilsenDepartment of Veterans Affairs Medical Center, Portland, OR, USA.
P Holland AldayDepartment of Veterans Affairs Medical Center, Portland, OR, USA.ORCID 0000-0002-0142-2438
J Stone DoggettDepartment of Veterans Affairs Medical Center, Portland, OR, USA.ORCID 0000-0002-6098-1520
Geoffrey I McFaddenSchool of Biosciences, The University of Melbourne, Parkville, VIC, Australia.ORCID 0000-0002-5351-1627
Christopher D GoodmanSchool of Biosciences, The University of Melbourne, Parkville, VIC, Australia.
Flaminia CatterucciaDepartment of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA.ORCID 0000-0003-3295-6683
Philip J RosenthalDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7953-7622
Michael K RiscoeDepartment of Veterans Affairs Medical Center, Portland, OR, USA.ORCID 0000-0002-1343-5279
Roland A CooperDepartment of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA, USA.
Alison RothExperimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.ORCID 0000-0001-6917-3485
Jane X KellyDepartment of Chemistry, Portland State University, Portland, OR, USA. kellyja@ohsu.edu.ORCID 0000-0001-8871-0207

Funding

Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) AI158533U.S. Department of Defense (United States Department of Defense) W81XWH2210494U.S. Department of Veterans Affairs (Department of Veterans Affairs) BX005674
6 · The paper itself

Abstract

Antimalarial therapeutics ideally should target all three major Plasmodium life cycle stages. Here we present an acridone antimalarial chemotype that is potent against blood, liver, and mosquito stages of malaria parasites. Attributes of lead candidate T111 include potent in vitro activity against cultured parasites, ex vivo activity against clinical isolates, oral single-dose cure in an asexual blood-stage rodent model, inhibition of sexual blood-stage parasites, activity against relapsing parasites in non-human primate liver cells, prevention of parasite development in mosquitoes, and synergy in combination with tafenoquine against blood- and liver-stage parasites. Analysis of parasites selected for resistance to T111 suggests inhibition of the mitochondrial electron transport chain, with a mechanism distinct from that of other antimalarials in use or under development. The safety profile of T111, including toxicology evaluations in rats, absence of hemolytic toxicity, and low genotoxicity and cardiotoxicity potential, demonstrates a favorable therapeutic index. Overall, T111 emerges as a promising candidate for treatment and prevention of malaria, with potential for single-dose cure of bloodstream infections, radical cure of liver infections, and interruption of transmission to mosquitoes.

Indexed as

AcridinesAcridonesAntimalarialsLife Cycle StagesMalariaPlasmodiumPlasmodium falciparumAminoquinolinesAnimalsFemaleHumansLiverMiceRatsAcridinesacridoneAcridonesAminoquinolinesAntimalarialstafenoquine

Identifiers

PMID41980931
PMCPMC13168289

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Registered trials

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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.