title: Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities.
abstract: 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 (1)H NMR, (13)C 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 µM). 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).
authors.forename: Insaf
authors.initials: I
authors.lastname: Filali
authors.forename: Anis
authors.initials: A
authors.lastname: Romdhane
authors.forename: Mansour
authors.initials: M
authors.lastname: Znati
authors.affiliation: 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. hich.benjannet@yahoo.fr.
authors.forename: Hichem B
authors.initials: HB
authors.lastname: Jannet
authors.affiliation: 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. jalloul.bouajila@univ-tlse3.fr.
authors.forename: Jalloul
authors.initials: J
authors.lastname: Bouajila
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D061565:Cycloaddition Reaction; D045325:HCT116 Cells; D006247:Harmine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D061986:MCF-7 Cells; D032443:Peganum; D066244:Proton Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D007555:Isoxazoles; D016859:Lipoxygenase Inhibitors; D013629:Tamoxifen; D006247:Harmine; D014969:Xanthine Oxidase