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Lookup NU author(s): Dr Joumaa Merza, Dr Mouhamed AlsaqatiORCiD, Dr Corinne Wills, Dr Paul Waddell, Dr Mark Ashton
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026. The polyfunctional pyrrole 3,5-dichloro-1H-pyrrole-2,4-dicarbaldehyde (2) was reacted with malononitrile and Meldrum’s acid in a regioselective manner to yield derivatives (4, 5, 6, 8, 9, and 10). Compound 8 was isolated and its structure was characterised by crystallography and 1 and 2D-1H, 13C-NMR spectroscopy. The biological effects of these derivatives were evaluated on differentiated SH-SY5Y human neuroblastoma cells, under control conditions and following Aβ exposure as an in vitro model of Alzheimer’s disease. MTT assays were performed to assess neuronal viability, and Annexin V staining was used to quantify apoptosis. Compounds 2 and 8 significantly increased cell viability in control differentiated neurons, suggesting a neurotrophic or protective effect. However, in Aβ-treated cells, all tested compounds, namely 5, 6, 8 and 2, reduced viability, indicating a possible interaction between our derivatives and Aβ-induced neurotoxicity. These findings reveal that certain polyfunctional pyrrole derivatives can differentially modulate neuronal survival depending on the cellular environment. This suggests that the neuronal cell death induced by Aβ in Alzheimer’s patients can be enhanced in the presence of those compounds. Since pyrrole scaffolds are present both in biologically essential molecules and in various environmental compounds, this dual action suggests their potential relevance in understanding the mechanisms of neurodegeneration and highlights the need for further mechanistic and translational studies to explore their impact on neurodegenerative disorders, including Alzheimer’s.
Author(s): Merza J, Alsaqati M, Wills C, Waddell PG, Ashton M
Publication type: Article
Publication status: Published
Journal: Cell Biochemistry and Biophysics
Year: 2026
Pages: Epub ahead of print
Online publication date: 10/06/2026
Acceptance date: 29/04/2026
Date deposited: 22/06/2026
ISSN (print): 1085-9195
ISSN (electronic): 1559-0283
Publisher: Springer Nature
URL: https://doi.org/10.1007/s12013-026-02090-4
DOI: 10.1007/s12013-026-02090-4
Data Access Statement: CCDC 2390238 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via [www.ccdc.cam.ac.uk/data\_request/cif] (http:/www.ccdc.cam.ac.uk/data_request/cif) , or by emailing [data\_request@ccdc.cam.ac.uk] (mailto: data_request@ccdc.cam.ac.uk) , or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033 Other data will be available on request. The ICC and apoptotic data are available from the corresponding author upon reasonable request.
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