Synthesis, characterization, and biological evaluation of N-methyl derivatives of norbelladine

Hashemian, S. M., Merindol, N., Paquin, A., Singh, A., Berthoux, L., Daoust, B. et Desgagné-Penix, I. (2024). Synthesis, characterization, and biological evaluation of N-methyl derivatives of norbelladine. Molecules, 29 (18). Article 4442. ISSN 1420-3049 DOI 10.3390/molecules29184442

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Résumé

Abstract

Norbelladine derivatives have garnered attention in recent years due to their diverse biological activities and pivotal role in the biosynthetic pathway of Amaryllidaceae alkaloids. This study reports the synthesis and biological evaluation of four O,N-methylated derivatives of norbelladine. These derivatives were synthesized through a three-step process: forming imine intermediates from benzaldehydes with tyramine, hydrogenating them to secondary amines, and N-methylating these amines. The products were purified and characterized by 1H and 13C NMR spectroscopy. Their biological activities were assessed by evaluating their ability to inhibit Alzheimer’s disease-related enzymes acetylcholinesterase and butyrylcholinesterase. Additionally, the cytotoxic activity of the novel derivatives was tested against cancer cell lines derived from hepatocarcinoma (Huh7), adenocarcinoma (HCT-8), and acute myeloid leukemia (THP-1) cells, and their antiviral properties against a human coronavirus (HCoV-OC43), a flavivirus (dengue virus), and a lentivirus (pseudotyped HIV-1). Docking analysis was performed to understand the impact of the N-methylation on their pharmacological relevance. The results indicate that while N-methylation does not significantly affect antiviral activity, it enhances butyrylcholinesterase inhibition for N-methylnorbelladine and 4′-O,N-dimethylnorbelladine. Overall, this work enhances our understanding of norbelladine derivatives, provides new tools for Alzheimer’s disease research, and lays the groundwork for future pharmaceutical developments.

Type de document:	Article
Mots-clés libres:	Amaryllidaceae alkaloids Tertiary amines Butyrylcholinesterase Acetylcholinesterase RNA virus Molecular docking
Date de dépôt:	22 avr. 2025 18:37
Dernière modification:	22 avr. 2025 18:37
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/11861

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