title: Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents.
abstract: A novel series of 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 3a-h were synthesized in a single step via condensation of carboxamide 2 with some aromatic aldehydes (presence of iodine). Treatment of aminopyrazole 1a with acetic anhydride afforded pyrazolopyrimidines 4 which on treatment with ethyl chloroacetate in refluxing dry DMF furnished a single product identified as ethyl 2-(3,6-dimethyl-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl) acetate 5. On the other hand, esterification of compound 6 with different alcohol, led to the formation of new esters linked pyrazolo[3,4-d]pyrimidinones hybrids 7a-f. The reaction of compound 2 with 3-propargyl bromide gave the compound 8 used as a dipolarophile to access to triazoles (4- and 5-regioisomers (9a-e) and (10a-e), respectively) via the 1,3-dipoar cycloaddition reaction. Finally, condensation reaction of aminopyrazole 1b with α-cyanocinnamonitiles gave the new pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitriles 11a-e. Structures of compounds were established on the basis of (1)H/(13)C NMR and ESI-HRMS. Compounds were screened for their cytotoxic (HCT-116 and MCF-7) and 5-lipoxygenase inhibition activities. The structure-activity relationship (SAR) was discussed.
authors.affiliation: Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia.
authors.forename: Ameur
authors.initials: A
authors.lastname: Rahmouni
authors.affiliation: Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia.
authors.forename: Sawssen
authors.initials: S
authors.lastname: Souiei
authors.affiliation: Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia; Université de Toulouse, Faculté de pharmacie de Toulouse, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique UMR CNRS 5623, Université Paul-Sabatier, 118 route de Narbonne, F-31062 Toulouse, France.
authors.forename: Mohamed Amine
authors.initials: MA
authors.lastname: Belkacem
authors.affiliation: Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia.
authors.forename: Anis
authors.initials: A
authors.lastname: Romdhane
authors.affiliation: Université de Toulouse, Faculté de pharmacie de Toulouse, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique UMR CNRS 5623, Université Paul-Sabatier, 118 route de Narbonne, F-31062 Toulouse, France. Electronic address: jalloul.bouajila@univ-tlse3.fr.
authors.forename: Jalloul
authors.initials: J
authors.lastname: Bouajila
authors.affiliation: Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l'Environnement, 5019 Monastir, Tunisia. Electronic address: hich.benjannet@yahoo.fr.
authors.forename: Hichem
authors.initials: H
authors.lastname: Ben Jannet
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D001094:Arachidonate 5-Lipoxygenase; C030986:pyrimidine
keywords: Anti-5-lipoxygenase; Anticancer; Pyrazoles; Pyrazolopyrimidines; Pyrimidines; Triazoles