title: Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine.
abstract: We synthesized two series of new hydrazide harmine derivatives. The reaction of harmine 1 with ethyl acetate chloride afforded the corresponding ethyl ester 2. The treatment of 2 with hydrazine hydrate gave the hydrazide 3 which further converted into hydrazones 4a-j and dihydrazides 5a-c. A series of new triazoles 7a-f has also been prepared from the suitable propargyl harmine 6. The synthesized derivatives were characterized by1H-NMR,13C-NMR, and HRMS and evaluated for their activities against MCF7, HCT116 OVCAR-3, acetylcholinesterase and 5-lipoxygenase. The most hydrazones derivatives 4a-j have a good cytotoxic activity against all cell lines, when 4a, 4d, 4f and 4 g are more active than 1 (against OVCAR-3 IC5016.7-2.5 μM). The compound 6 was the most active (IC50=1.9 μM) against acetylcholinesterase. Some compounds exhibited significant activity against 5-lipoxygenase (IC50=30.9-63.1 μM).
authors.affiliation: a Laboratoire de Chimie Hétérocyclique , Produits Naturels et Réactivité (CHPNR), Equipe Chimie Médicinale et Produits Naturels Département de Chimie, Faculté des Sciences de Monastir, Université de , Monastir , Tunisie , and.|b Laboratoire des IMRCP UMR CNRS , Faculté de pharmacie de Toulouse, Université de Toulouse, Université Paul-Sabatier , Toulouse , France.
authors.forename: Insaf
authors.initials: I
authors.lastname: Filali
authors.affiliation: a Laboratoire de Chimie Hétérocyclique , Produits Naturels et Réactivité (CHPNR), Equipe Chimie Médicinale et Produits Naturels Département de Chimie, Faculté des Sciences de Monastir, Université de , Monastir , Tunisie , and.|b Laboratoire des IMRCP UMR CNRS , Faculté de pharmacie de Toulouse, Université de Toulouse, Université Paul-Sabatier , Toulouse , France.
authors.forename: Mohamed Amine
authors.initials: MA
authors.lastname: Belkacem
authors.affiliation: a Laboratoire de Chimie Hétérocyclique , Produits Naturels et Réactivité (CHPNR), Equipe Chimie Médicinale et Produits Naturels Département de Chimie, Faculté des Sciences de Monastir, Université de , Monastir , Tunisie , and.
authors.forename: Aymen
authors.initials: A
authors.lastname: Ben Nejma
authors.affiliation: b Laboratoire des IMRCP UMR CNRS , Faculté de pharmacie de Toulouse, Université de Toulouse, Université Paul-Sabatier , Toulouse , France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Souchard
authors.affiliation: a Laboratoire de Chimie Hétérocyclique , Produits Naturels et Réactivité (CHPNR), Equipe Chimie Médicinale et Produits Naturels Département de Chimie, Faculté des Sciences de Monastir, Université de , Monastir , Tunisie , and.
authors.forename: Hichem
authors.initials: H
authors.lastname: Ben Jannet
authors.affiliation: b Laboratoire des IMRCP UMR CNRS , Faculté de pharmacie de Toulouse, Université de Toulouse, Université Paul-Sabatier , Toulouse , France.
authors.forename: Jalloul
authors.initials: J
authors.lastname: Bouajila
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; 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; D006247:Harmine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D016859:Lipoxygenase Inhibitors; D006247:Harmine; D008084:Lipoxygenase; D000110:Acetylcholinesterase
keywords: 5-lipoxygenase; Acetylcholinesterase; cytotoxic; hydrazide; triazoles