Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 23, Pages 7873-7877Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm901131m
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- MIUR, Rome (PRIN)
- University of Bologna (RFO)
- Polo Scientifico-Didattico di Rimini
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Naphthalimmide (NI) and 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity. NDI derivatives 1-9 were more cytotoxic than the corresponding NI derivatives 10-18. The molecular mechanisms of 1 and 2 were investigated in comparison to mitonafide. They interacted with DNA, were not topoisomerase II alpha poisons, triggered caspase activation, caused p53 protein accumulation, and down-regulated AKT survival. Furthermore, 1 and 2 caused a decrease of ERK1/2 and, unlike mitonafide, inhibited ERKs phosphorylation.
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