Synthesis and evaluation of nitroheterocyclic aromatic adamantane amides with trypanocidal activity. Part II
In this article, we report the design, synthesis, and biological evaluation of a new series of nitroheterocyclic aromatic adamantane amides targeting trypanosomes. These compounds feature diverse substituents on the adamantane scaffold, variations in side chain linker length, and a range of nitroheterocyclic moieties. This work represents a continuation of our previous efforts, with a particular focus on elucidating the structural and functional role of the linker connecting the phenyladamantane core to the nitroheterocyclic ring. The structure-activity relationship data underscore the importance of strategic modifications in enhancing the pharmacological profile of these compounds against trypanosome parasites. Further modifications are recommended to optimize the physicochemical properties of the current derivatives to improve intracellular targeting of trypanosomatids, an important clinical stage in their life cycle.
Authors
- Nuno Santarém (ORCID: https://orcid.org/0000-0003-4973-9933)
- Martin C. Taylor (ORCID: https://orcid.org/0000-0003-4147-0693)
- Ioannis Papanastasiou (ORCID: https://orcid.org/0000-0001-6974-2561)
- Thomas Mavromoustakos (ORCID: https://orcid.org/0000-0001-5309-992X)
- Theodora Calogeropoulou (ORCID: https://orcid.org/0000-0002-3369-5393)
- Markos‐Orestis Georgiadis (ORCID: https://orcid.org/0000-0002-9804-9675)
- Richard L. Atherton (ORCID: https://orcid.org/0000-0001-8633-4535)
- John M. Kelly (ORCID: https://orcid.org/0000-0003-4305-5258)
- Angeliki‐Sofia Foscolos (ORCID: https://orcid.org/0000-0001-8123-5060)
- Anabela Cordeiro‐da‐Silva (ORCID: https://orcid.org/0000-0003-2392-6087)
- Andrew Tsotinis (ORCID: https://orcid.org/0000-0002-4334-4810)
- Maria Billia
Institutions
- University of London (GB)
- Northeastern University (US)
- 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)
- National Hellenic Research Foundation (GR)
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto (PT)
Publication Details
- Journal
- RSC Medicinal Chemistry
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1039/d5md00527b
- Primary Topic
- Eicosanoids and Hypertension Pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Hellenic Foundation for Research and Innovation
- Fundação para a Ciência e a Tecnologia