Synthesis and Evaluation of Nitroheterocyclic Aromatic Adamantanohydrazones with Trypanocidal Activity. Part III
Extending our research on the design, synthesis, and pharmacological evaluation of antitrypanosomatid nitroheterocyclic aromatic adamantanes, we have identified hydrazone derivatives conjugated with 5-nitrothiophene that have submicromolar activity against trypanosomes. Key structural features, namely, the incorporation of the adamantane ring into the skeleton of the new compounds, the nature and the length of the hydrazone linker, and the nitroheterocycle moiety were evaluated to optimize both efficacy and safety profiles. It is also shown that these compounds function as prodrugs that are bioactivated by parasite-specific nitroreductase enzymes, primarily NTR-1. These findings suggest that nitroheterocyclic aromatic adamantanohydrazones represent promising candidates for further development as antitrypanosomal agents.
Authors
- Martin C. Taylor (ORCID: https://orcid.org/0000-0003-4147-0693)
- Ioannis Papanastasiou (ORCID: https://orcid.org/0000-0001-6974-2561)
- Theodora Calogeropoulou (ORCID: https://orcid.org/0000-0002-3369-5393)
- Susan Wyllie (ORCID: https://orcid.org/0000-0001-8810-5605)
- Konstantina Stavropoulou (ORCID: https://orcid.org/0009-0008-4828-5339)
- John M. Kelly (ORCID: https://orcid.org/0000-0003-4305-5258)
- Angeliki‐Sofia Foscolos (ORCID: https://orcid.org/0000-0001-8123-5060)
- Andrew Tsotinis (ORCID: https://orcid.org/0000-0002-4334-4810)
- Anabela Cordeiro da Silva
- Nuno Santarém
Institutions
- Massachusetts College of Pharmacy and Health Sciences (US)
- University of Dundee (GB)
- Universidade do Porto (PT)
- National and Kapodistrian University of Athens (GR)
- National Centre of Scientific Research "Demokritos" (GR)
- London School of Hygiene & Tropical Medicine (GB)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- National Hellenic Research Foundation (GR)
- Department of Biological Sciences (RU)
- Interaction Design (United Kingdom) (GB)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2026-06-17
- DOI
- https://doi.org/10.1021/acsinfecdis.6c00201
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Dundee
- Wellcome Trust
- Hellenic Academic Libraries Link
- European Cooperation in Science and Technology
- Hellenic Foundation for Research and Innovation
- Foundation for Science and Technology
- Fundação para a Ciência e a Tecnologia