2. Academic Validation
  3. Design, synthesis, and biological evaluation of substituted naphthalene imides and diimides as anticancer agent

Design, synthesis, and biological evaluation of substituted naphthalene imides and diimides as anticancer agent

  • J Med Chem. 2009 Dec 10;52(23):7873-7. doi: 10.1021/jm901131m.
Vincenzo Tumiatti 1,  Andrea Milelli,  Anna Minarini,  Marialuisa Micco,  Anna Gasperi Campani,  Laura Roncuzzi,  Daniela Baiocchi,  Jessica Marinello,  Giovanni Capranico,  Maddalena Zini,  Claudio Stefanelli,  Carlo Melchiorre
Affiliations

Affiliation

  • 1 Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. vincenzo.tumiatti@unibo.it
PMID: 19954251 DOI: 10.1021/jm901131m
Abstract

Naphthalimmide (NI) and 1,4,5,8-naphthalentetracarboxylic 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 IIalpha 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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