Design, synthesis, and in vitro evaluation of new naphthylnitrobutadienes with potential antiproliferative activity: Toward a structure/activity correlation

Giovanni Petrillo, Maria A. Mariggiò, Cinzia Aiello, Cinzia Cordazzo, Carla Fenoglio, Stefano Morganti, Michela Croce, Egon Rizzato, Domenico Spinelli, Massimo Maccagno, Lara Bianchi, Claudia Prevosto, Cinzia Tavani, Maurizio Viale

Research output: Contribution to journalArticle

Abstract

On the grounds of previous encouraging results on the antitumor activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1), we have designed and synthesized two new molecules [(1E,3E)-1,4-bis(4-carboxy-1-naphthyl)-2,3-dinitro-1,3-butadiene (2) and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (3)] characterized by a common naphthylnitrobutadiene array but with different structural properties, with the aim of approaching to some structure-activity correlation. When 2 and 3 were analyzed in vitro for their inhibition of cell proliferation and pro-apoptotic properties, the carboxyderivative 2 did not furnish appreciable results. In contrast, 3 (which contains only one of the two naphthylnitroethenyl moieties of the original compound 1) showed remarkable activities in the range of micromolar concentrations (in six over eight cell lines its IC50s are in the 1-3 μM range), with a significant improvement compared to 1. In particular, 3 proved able to bind to DNA, to upregulate p53, to block cells in the G2/M phase of their cycle, and to induce apoptosis. Thus, very interestingly, the performance of 3 with respect to 1 shows that a single 1-(1-naphthyl)-2-nitroethene moiety is able to ensure better (on four out of eight of the cell lines tested) or comparable levels of activity. This result suggests that the 'molecular-simplification strategy' could furnish a useful instrument for future design in our antitumor research.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

Keywords

  • Antiproliferative activity
  • Mechanism of action
  • Molecular-simplification strategy
  • Naphthylnitrobutadienes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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  • Cite this

    Petrillo, G., Mariggiò, M. A., Aiello, C., Cordazzo, C., Fenoglio, C., Morganti, S., Croce, M., Rizzato, E., Spinelli, D., Maccagno, M., Bianchi, L., Prevosto, C., Tavani, C., & Viale, M. (2008). Design, synthesis, and in vitro evaluation of new naphthylnitrobutadienes with potential antiproliferative activity: Toward a structure/activity correlation. Bioorganic and Medicinal Chemistry, 16(1), 240-247. https://doi.org/10.1016/j.bmc.2007.09.042