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ORIGINAL RESEARCH ARTICLE

Metabolomic profiling of aluminum chloride-intoxicated rats treated with novel dual inhibitors targeting acetylcholinesterase for Alzheimer’s therapy

Samir H. I. Haggag1 ,  Noha S. Hussein1 ,  Abdel-Hamid Z. Abdel-Hamid1 ,  Hanan F. Aly1* ,  Eman A. Younis1 ,  Asmaa F. Aboul-Naser1 ,  Maha Z. Rizk1
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1 Department of Therapeutic Chemistry, Pharmaceutical Industries Research Institute, National Research Centre, Dokki, Cairo, Egypt
Advanced Neurology, 025510129 https://doi.org/10.36922/AN025510129
Received: 20 December 2025 | Revised: 25 March 2026 | Accepted: 1 April 2026 | Published online: 12 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Millions of elderly people worldwide have Alzheimer’s disease (AD), a complex and progressive neurological illness. AD can only be definitively diagnosed postmortem by examining brain tissue obtained during autopsy, which makes detection and intervention challenging. Therefore, identifying specific metabolites as potential metabolic biomarkers associated with AD risk is crucial. For a comprehensive understanding of the role of metabolic biomarkers in AD etiology, we performed metabolomics-based gas chromatography–mass spectrometry to characterize serum metabolite alterations in rats with AlCl3-induced AD-like neurotoxicity. We evaluated metabolite levels across five experimental groups (10 rats per group). We further conducted metabolic profiling to identify metabolomic features associated with AD risk and to assess the therapeutic effects of newly synthesized compounds, including benzofuran-derivative-7 (MP19) and coumarin-3 (MP27). Four metabolites identified in this study provided strong discriminative power for AD diagnosis, offering a potential approach for biomarker detection that may enhance patient diagnosis and prognosis in the future. This study provides new insights into the etiology, early detection, and potential therapy for AD, involving blood-based metabolic biomarkers that warrant further investigation.

Keywords
Alzheimer; Metabolomics
Gas chromatography–mass spectrometry
Metabolic biomarkers
Benzofuran
Coumarin derivatives
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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