title: Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities.
abstract: In our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively).
authors: Laboratoire de Chimie Hétérocyclique, Département de Chimie, Faculté des Sciences de Monastir, Produits Naturels et Réactivité (CHPNR), Equipe Chimie Médicinale et Produits Naturels, Université de Monastir , Monastir Tunisie , France and.
authors: Insaf
authors: I
authors: Filali
authors: Jalloul
authors: J
authors: Bouajila
authors: Mansour
authors: M
authors: Znati
authors: Fatima
authors: F
authors: Bousejra-El Garah
authors: Hichem
authors: H
authors: Ben Jannet
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006247:Harmine / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D007555:Isoxazoles; D016859:Lipoxygenase Inhibitors; D006247:Harmine; D001094:Arachidonate 5-Lipoxygenase; D000110:Acetylcholinesterase
keywords: 1,3-dipolar cycloaddition; Peganum harmala; anti-5-lipoxygenase; anti-acetylcholinesterase; anti-cancer; harmine; oxazolines