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
  • 1. Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. [email protected]
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.