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Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities

[ Vol. 12 , Issue. 2 ]


Insaf Filali, Anis Romdhane, Mansour Znati, Hichem B. Jannet and Jalloul Bouajila   Pages 184 - 190 ( 7 )


Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by 1H NMR, 13C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3±1.9% at 100 M). Compound 2 exhibited the best anti-AChE activity (IC50=1.9±1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0±0.3 µM (3a) and IC50=6.3±0.4 µM (3b) against HCT 116 cells, IC50=5.0±1.0 µM (3d) against MCF7 cells).


Peganum harmala, harmine, isoxazoles, anti-inflammatory, anti-xanthine oxidase, anticancer.


Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivite (CHPNR), Equipe Chimie Médicinale et Produits Naturels Département de Chimie, Faculté des Sciences de Monastir, Université de, Monastir, Avenue de l’Environnement, 5019 Monastir Tunisie., Université de Toulouse, Université Paul- Sabatier, Faculté de pharmacie de Toulouse, Laboratoire des IMRCP UMR CNRS 5623, 118 route de Narbonne, F-31062 Toulouse, France.

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