Design, synthesis, and biological evaluation of substituted naphthalene imides and diimides as anticancer agent.
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.
Tumiatti
Vincenzo
V
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. vincenzo.tumiatti@unibo.it
Milelli
Andrea
A
Minarini
Anna
A
Micco
Marialuisa
M
Gasperi Campani
Anna
A
Roncuzzi
Laura
L
Baiocchi
Daniela
D
Marinello
Jessica
J
Capranico
Giovanni
G
Zini
Maddalena
M
Stefanelli
Claudio
C
Melchiorre
Carlo
C
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007094:Imides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D009281:Naphthalenes / Q000737:chemistry*; D059003:Topoisomerase Inhibitors
D000970:Antineoplastic Agents; D007094:Imides; D009281:Naphthalenes; D059003:Topoisomerase Inhibitors; C031721:naphthalene; D004247:DNA