Collaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments

Neglected tropical diseases (NTDs) make up a diverse group of debilitating illnesses disproportionately affecting impoverished communities in tropical and subtropical regions. Despite their significant global health burden, they are often overshadowed by more prominent diseases, resulting in a critical lack of investment in the research and development of new treatments. A renewed focus on NTDs is, therefore, urgently needed, particularly in terms of novel therapeutic strategies. The Open Synthesis Network, launched by DNDi and partner institutions in 2016, is an innovation powerhouse that taps into the potential of students to help drive the discovery of new drugs for patients living with NTDs. We present the results of student-led work into the development of a series of aminopyrazoles for Chagas disease, a multisystemic disease caused by the <i>Trypanosoma cruzi</i> parasite. Seventy-four compounds were synthesized by undergraduate and postgraduate students from six universities from Brazil, Ghana, Germany, USA, and UK, illustrating that open innovation and collaboration for education can drive drug discovery forward. Early evaluation of the structure-activity relationships identified a range of potent hit compounds with selectivity for <i>T. cruzi</i> and no observable cytotoxicity.

Authors

Institutions

Publication Details

Journal
ACS Infectious Diseases
Published
2025-08-11
DOI
https://doi.org/10.1021/acsinfecdis.5c00481
Primary Topic
Trypanosoma species research and implications
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Collaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments

Kayla Reid, João Lucas dos S. Avelar, Lawrence J. Wysocki, An Matheeussen et al.
ACS Infectious Diseases
Trypanosoma species research and implications
article

Collaborative Synthesis for Neglected Diseases through the Open Synthesis Network: Structure–Activity Relationships of Arylaminopyrazoles as Chagas Disease Treatments

Kayla Reid, João Lucas dos S. Avelar, Lawrence J. Wysocki, An Matheeussen, Matthew Martin, Finan Johns, Helen C. Jackson, Justus F. Ködel, Dhruvi Patel, Lı́dia Moreira Lima, Emma J. Jones, Rita Maccarone, Brian Chan, Luiza R. Cruz, Ignatius Nguyen, Д. В. Калинин, Chase C. Smith, Norman C.W. Wong, Emma Waddell, Andrew Nortcliffe, Bernhard Wünsch, Natascha Van Pelt, Donald Hsu, S. Roy, P.R. Knight, Hilary Page, R. C. Canby, Kanchan Bhardwaj, J.J. den Otter, Matthew F. Grady, Guy Caljon, Hyejin Lee, Joseph A. Driscoll, E Cartwright, Sophie C. Warner, Angus W. Thomson, Jamie Hutchinson, K. R. Samaddar, Zigli Abdulai, Lukas Imberg, Charles A. Clifford, Nicholas Breitkreuz, Noor Zehra Shabbir, Cristiane Aparecida-Silva, Bernhard Biersack, Benjamin Perry, M.Z.H. Mahmud, A. J. SMITHIES, Carolyn J. Friel, Richard K. Amewu, Shannon A Cordell, Aaron Keal, Tobias Winge, Seung Hyun Kim, Candice Yong, Anna Bertram, Christopher C. Nolan, P.M. Shevlin, Jack Tinker, J Anderson, Alexander Uner, William J Bowley, William J Donker, Lauren Higginbotham, Natasha Agbo, Ceren Kardeşler, Libby Keel, Luke Kumeta, Faye Astley, Lucy Noyes, Angela N. W Ntuwa, Wiktoria Obarska, Owen Oldham, Edna Onyiuke, Callum Sinclair-Wright, Owen Atkinson-Evans, Hamis Wagwa, Claire Walthorne, Zaria Zaheen
article en

Abstract

Neglected tropical diseases (NTDs) make up a diverse group of debilitating illnesses disproportionately affecting impoverished communities in tropical and subtropical regions. Despite their significant global health burden, they are often overshadowed by more prominent diseases, resulting in a critical lack of investment in the research and development of new treatments. A renewed focus on NTDs is, therefore, urgently needed, particularly in terms of novel therapeutic strategies. The Open Synthesis Network, launched by DNDi and partner institutions in 2016, is an innovation powerhouse that taps into the potential of students to help drive the discovery of new drugs for patients living with NTDs. We present the results of student-led work into the development of a series of aminopyrazoles for Chagas disease, a multisystemic disease caused by the <i>Trypanosoma cruzi</i> parasite. Seventy-four compounds were synthesized by undergraduate and postgraduate students from six universities from Brazil, Ghana, Germany, USA, and UK, illustrating that open innovation and collaboration for education can drive drug discovery forward. Early evaluation of the structure-activity relationships identified a range of potent hit compounds with selectivity for <i>T. cruzi</i> and no observable cytotoxicity.

ACS Infectious DiseasesVol. 11(9)
Universidade Federal do Rio de Janeiro (BR), Drugs for Neglected Diseases Initiative (CH), University of Ghana (GH), University of Nottingham (GB), University of Antwerp (BE), Massachusetts College of Pharmacy and Health Sciences (US), University of Münster (DE), Centro Universitário da Cidade (BR), University of Bayreuth (DE)
National Institute of General Medical Sciences, U.S. National Library of Medicine
Industry, innovation and infrastructure
Openalex Percentile: Top 72%
Trypanosoma species research and implications
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.