title: Dihydrithieno[2,3-b]naphto-4,9-dione analogues as anticancer agents: Synthesis and in cell pharmacological studies.
abstract: The synthesis of a series of highly functionalized DNTQ-based derivatives is described. In vitro, most of the compounds exerted a cytotoxic effect against several tumour cell lines comparable to or greater than that of doxorubicin. Here we demonstrate that compound 14, the less cardiotoxic compound of this series, induced cell differentiation and was distributed mainly in the cytoplasm in the human glioblastoma LN229 cell line. Moreover, compound 14 reduced both cellular glucose uptake and serine/threonine kinase AKT expression, and triggered cell apoptosis. These findings suggest that highly functionalized DTNQ-based derivatives are promising pharmacological tools for the study of human solid tumours.
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.affiliation: Department of Pharmaceutical Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Musella
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Di Sarno
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Ostacolo
authors.affiliation: Department of Sciences, University of Basilicata, Via dell'Ateneo Lucano 10, 85100 Potenza, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Manfra
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via Luigi De Crecchio 7, 80138 Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vanacore
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Via Luigi De Crecchio 7, 80138 Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy. Electronic address: imgomez@unina.it.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Gomez-Monterrey
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; C000608145:dihydrithieno(2,3-b)naphto-4,9-dione
keywords: Anti-tumor agents; Apoptosis; Cellular glucose uptake; Quinone derivatives