title: Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities.
abstract: The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a-e has been accomplished by reaction of 2-acetonitrile derivatives 1a-e with hydroxylamine. Cyclocondensation reaction of precursors 2a-e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a-e, 4a-e, and 5a-e, respectively. On the other hand, the reaction of precursors 2a-e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a-e which evolve under reflux of toluene to the new oxadiazoles 7a-e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i) 5a was the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii) 2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while 2e is highly selective against OVCAR-3 (IC50 = 10 μM).
authors.affiliation: a Laboratoire De Chimie Hétérocyclique , Produits Naturels Et Réactivité (CHPNR), Equipe Chimie Médicinaleet Produits Naturels, Département De Chimie, Faculté Des Sciences De Monastir, Université De Monastir , Monastir Tunisie , France .
authors.forename: Abderrahim Ben
authors.initials: AB
authors.lastname: Saïd
authors.affiliation: a Laboratoire De Chimie Hétérocyclique , Produits Naturels Et Réactivité (CHPNR), Equipe Chimie Médicinaleet Produits Naturels, Département De Chimie, Faculté Des Sciences De Monastir, Université De Monastir , Monastir Tunisie , France .
authors.forename: Anis
authors.initials: A
authors.lastname: Romdhane
authors.affiliation: b Centre De Recherche De Gif, Institut De Chimie Des Substances Naturelles, CNRS , Gif-sur-Yvette Cedex , France , and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Elie
authors.affiliation: b Centre De Recherche De Gif, Institut De Chimie Des Substances Naturelles, CNRS , Gif-sur-Yvette Cedex , France , and.
authors.forename: David
authors.initials: D
authors.lastname: Touboul
authors.affiliation: a Laboratoire De Chimie Hétérocyclique , Produits Naturels Et Réactivité (CHPNR), Equipe Chimie Médicinaleet Produits Naturels, Département De Chimie, Faculté Des Sciences De Monastir, Université De Monastir , Monastir Tunisie , France .
authors.forename: Hichem Ben
authors.initials: HB
authors.lastname: Jannet
authors.affiliation: c Faculté De Pharmacie De Toulouse , Laboratoire Des Interactions Moléculaires Et Réactivité Chimique Et Photochimique UMR CNRS 5623, Université Paul-Sabatier, Université De Toulouse , Toulouse , France.
authors.forename: Jalloul
authors.initials: J
authors.lastname: Bouajila
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008084:Lipoxygenase / Q000187:drug effects*; D066244:Proton Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013025:Glycine max / Q000201:enzymology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D008084:Lipoxygenase; D014969:Xanthine Oxidase
keywords: Amidoximes; cytotoxic activity; soybean lipoxygenase inhibition; triazolo[1,5-c]pyrimidine,1,2,4-oxadiazole; xanthine oxidase inhibition