title: Design, synthesis, and cytotoxic evaluation of acyl derivatives of 3-aminonaphtho[2,3-b]thiophene-4,9-dione, a quinone-based system.
abstract: A series of 3-acyl derivatives of the dihydronaphtho[2,3-b]thiophen-4,9-dione system were studied with respect to cytotoxicity and topoisomerase II inhibitory activity. These analogues were designed as electron-deficient anthraquinone analogues with potential intercalation ability. Derivatives 3-(diethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11m) and 3-(2-(dimethylamino)ethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho[2,3-b]thiophen-3-yl)propanamide (11p) showed a high efficacy in cell lines that were highly resistant to treatment with doxorubicin, such as MDA-MB435 (melanoma), IGROV (ovarian), and SF-295 (glioblastoma) human cell lines. Both compounds inhibit topoisomerase II mediated relaxation of DNA, while only 11p incites arrest at the S phase in Caco-2 cells, inducing a delay of cell cycle progression and an increase of cell differentiation. The ability of these derivatives to modulate small heat shock proteins and cardiotoxicy effects was also explored. In addition, the DNA-binding properties of these compounds were investigated and discussed.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Claudio
authors.initials: C
authors.lastname: Aquino
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Ilaria
authors.initials: I
authors.lastname: Granata
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
authors.forename: Ilaria
authors.initials: I
authors.lastname: Scognamiglio
authors.forename: M Rosaria
authors.initials: MR
authors.lastname: Rusciano
authors.forename: Angela Serena
authors.initials: AS
authors.lastname: Maione
authors.forename: Maddalena
authors.initials: M
authors.lastname: Illario
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Bruno
authors.initials: B
authors.lastname: Maresca
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C561051:3-(2-(dimethylamino)ethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho(2,3-b)thiophen-3-yl)propanamide; C561050:3-(diethylamino)-N-(4,9-dioxo-4,9-dihydronaphtho(2,3-b)thiophen-3-yl)propanamide; D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins; D009281:Naphthalenes; D009285:Naphthoquinones; D013876:Thiophenes; D004317:Doxorubicin; D004247:DNA