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
Design, Synthesis, and Cytotoxic Evaluation of AcylDerivatives of 3-Aminonaphtho[2,3-b]thiophene-4,9-dione, a Quinone-Based System / GOMEZ MONTERREY, ISABEL MARIA; P., Campiglia; Aquino, Claudio; A., Bertamino; I., Granata; Carotenuto, Alfonso; Brancaccio, Diego; P., Stiuso; I., Scognamiglio; M. R., Rusciano; A. S., Maione; Illario, Maddalena; Grieco, Paolo; B., Maresca; Novellino, Ettore. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 54:12(2011), pp. 4077-4091. [10.1021/jm200094h]
Design, Synthesis, and Cytotoxic Evaluation of AcylDerivatives of 3-Aminonaphtho[2,3-b]thiophene-4,9-dione, a Quinone-Based System
GOMEZ MONTERREY, ISABEL MARIA;AQUINO, CLAUDIO;CAROTENUTO, ALFONSO;BRANCACCIO, DIEGO;ILLARIO, MADDALENA;GRIECO, PAOLO;NOVELLINO, ETTORE
2011
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 discussedI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
