Some NI and NDI derivatives possessing one or two basic side chains were synthesized and assayed for their antiproliferative activity and molecular mechanisms. Our results indicated that NDI derivatives 1-8 resulted more effective than the corresponding NI derivatives 9-18. The most potent compounds of the series resulted 2 which was choosen, together with the mitonafide corresponding NDI compound 1, for further investigations about their cytotoxic activity. All these compounds, together with the reference compound mitonafide, showed the ability to intercalate DNA, trigger caspase activation, cause accumulation of p53 protein and downregulate the survival kinase AKT. Furthermore mitonafide, as 1 and 2, caused a decrease of ERK1/2 but, differently by 1 and 2, it did not inhibit their phosphorylation.

DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF SUSTITUTED NAPHTHALENE IMIDES AND DIIMIDES AS ANTICANCER AGENT

TUMIATTI, VINCENZO;MILELLI, ANDREA;MINARINI, ANNA;MICCO, MARIALUISA;GASPERI CAMPANI, ANNA;RONCUZZI, LAURA;BAIOCCHI, DANIELA;MARINELLO, JESSICA;CAPRANICO, GIOVANNI;ZINI, MADDALENA;STEFANELLI, CLAUDIO;MELCHIORRE, CARLO
2009

Abstract

Some NI and NDI derivatives possessing one or two basic side chains were synthesized and assayed for their antiproliferative activity and molecular mechanisms. Our results indicated that NDI derivatives 1-8 resulted more effective than the corresponding NI derivatives 9-18. The most potent compounds of the series resulted 2 which was choosen, together with the mitonafide corresponding NDI compound 1, for further investigations about their cytotoxic activity. All these compounds, together with the reference compound mitonafide, showed the ability to intercalate DNA, trigger caspase activation, cause accumulation of p53 protein and downregulate the survival kinase AKT. Furthermore mitonafide, as 1 and 2, caused a decrease of ERK1/2 but, differently by 1 and 2, it did not inhibit their phosphorylation.
JOURNAL OF MEDICINAL CHEMISTRY
Tumiatti V; Milelli A ; Minarini A; Micco M; Gasperi-Campani A; Roncuzzi L; Baiocchi D; Marinello J; Capranico G; Zini M; Stefanelli C; Melchiorre C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/78511
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