• DNDi - Best Science for the Most Neglected 20 Years
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • Pandemic Preparedness
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies and IP
      • Children’s health
      • Gender equity
      • Climate change
      • AI and new technologies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • Dengue Alliance
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Switzerland
      • DNDi DRC
      • DNDi Eastern Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
      • Podcasts, radio & TV
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
      • Our prizes and awards
      • Our story: 20 years of DNDi
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
DNDi - Best Science for the Most Neglected 20 Years
  • DNDi - Best Science for the Most Neglected 20 Years
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • Pandemic Preparedness
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies and IP
      • Children’s health
      • Gender equity
      • Climate change
      • AI and new technologies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • Dengue Alliance
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Switzerland
      • DNDi DRC
      • DNDi Eastern Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
      • Podcasts, radio & TV
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
      • Our prizes and awards
      • Our story: 20 years of DNDi
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
Home > Scientific articles
Sep 2020
Share on twitter
Share on facebook
Share on linkedin
Share on email
Share on print

Re-evaluating pretomanid analogues for Chagas disease: Hit-to-lead studies reveal both in vitro and in vivo trypanocidal efficacy

European Journal of Medicinal Chemistry

by Thompson AM, O’Connor PD, Marshall AJ, Francisco AF, Kelly JM, Riley J, Read KD, Perez CJ, Cornwall S, Thompson RCA, Keenan M, White KL, Charman SA, Zulfiqar B, Sykes ML, Avery VM, Chatelain E, Denny WA. European Journal of Medicinal Chemistry 2020; 207:112849. doi: 10.1016/j.ejmech.2020.112849

Summary: A 900-compound library of nitroimidazole derivatives related to pretomanid, a treatment for highly challenging cases of tuberculosis, was screened against the causative agent of Chagas disease, Trypanosoma cruzi. Several structurally diverse hits with an unknown mode of action were identified. Following initial profiling, a first proof-of-concept in vivo study was undertaken, in which once daily oral dosing of a 7-substituted 2-nitroimidazooxazine analogue suppressed blood parasitemia to low or undetectable levels, although sterile cure was not achieved. Limited hit expansion studies laid the foundation for a more in-depth assessment of the best leads. Comparative appraisal of one preferred lead in a chronic infection mouse model provided the first definitive evidence of (partial) curative efficacy with this promising nitroimidazooxazine class.

access the article
Drug discovery Chagas disease

Latest scientific articles

Loading...
Scientific articles
27 Nov 2023

A simulation-based method to inform serosurvey designs for estimating the force of infection using existing blood samples

PLOS Computational Biology
Scientific articles
21 Nov 2023

Safety and efficacy of paromomycin/ miltefosine/ liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study

PLOS Neglected Tropical Diseases
Scientific articles
21 Nov 2023

Clinical use of molecular methods for Trypanosoma cruzi infection in endemic and non-endemic countries: Benefits, limitations and challenges

Frontiers in Parasitology
Scientific articles
10 Nov 2023

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

Science
VIEW ALL

Stay connected

Get our latest news, personal stories, research articles, and job opportunities. 

DNDi - Best Science for the Most Neglected 20 Years
Facebook-f
Twitter
Instagram
Linkedin-in
Youtube
International non-profit developing safe, effective, and affordable treatments for the most neglected patients.

Learn more

  • Diseases
  • Neglected tropical diseases
  • R&D portfolio
  • Policy advocacy

Get in touch

  • Our offices
  • Contact us
  • Integrity Line

Support us

  • Donate
  • Subscribe to eNews

Work with us

  • Join research networks
  • Jobs
  • RFPs
  • Terms of Use   
  •   Acceptable Use Policy   
  •   Privacy Policy   
  •   Cookie Policy   
  •   Our policies   

  • Except for images, films and trademarks which are subject to DNDi’s Terms of Use, content on this site is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Switzerland License