Cytotoxicity and cell death mechanisms induced by a Novel Bisnaphthalimidopropyl Derivative against the NCI-H460

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 15, 10 Issues, 2015

Download PDF Flyer

Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 22nd of 58 in Chemistry, Medicinal
  • 85th of 202 in Oncology

Submit Abstracts Online Submit Manuscripts Online

Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.939
5 - Year: 3.37

Cytotoxicity and cell death mechanisms induced by a Novel Bisnaphthalimidopropyl Derivative against the NCI-H460

Author(s): Raquel T. Lima, Gemma A. Barron, Joanna A. Grabowska, Giovanna Bermano, Simranjeet Kaur, Nilanjan Roy, M. Helena Vasconcelos and Paul Kong Thoo Lin


Some polyamine derivatives, namely the bisnaphthalimidopropyl polyamines (BNIPPs) may have potential as anticancer drugs. Indeed, previous work from some of us had shown that the ability of these molecules to bind to DNA may contribute to their cytotoxicity. However, their precise mode of action has not been fully understood. In the present work, we report for the first time the effect of the previously synthesised compounds, BNIPDaCHM and NPA, together with a new BNIP derivative (BNIP-3,4-DaDPM) in the in vitro growth of a non-small cell lung cancer (NCI-H460). In addition, for the most potent compound (BNIPDaCHM), its activity as sirtuin inhibitor was investigated in vitro and further confirmed in silico.

Results in the NCI-H460 cells showed that, from the compounds tested, BNIPDaCHM was the most potent (GI50 of 1.3 µM). In addition, a concentration-dependent alteration in the normal NCI-H460 cell cycle profile was observed following treatment with BNIPDaCHM as well as an increase in the sub-G1 peak (suggestive of apoptotis). This effect was further supported by Annexin V/PI staining and by analysing the expression of proteins related to apoptosis (cleaved PARP and Caspase-3) by Western blot. It was also observed that BNIPDaCHM inhibited the activity of SIRT2 in vitro, but not of SIRT1. Accordingly, this compound also caused a small increase in tubulin acetylation in NCI-H460 cells. To determine the binding potential of BNIPDaCHM on hSIRT2 and to further validate its inhibitory action, in silico docking studies were carried out, which revealed that BNIPDaCHM is composed of an entirely new SIRT2-inhibiting structural scaffold. In conclusion, this study indicates that BNIP derivatives with a novel structural backbone, such as BNIPDaCHM, may have potential as building blocks for novel antitumour agents which might selectively bind to hSIRT-2.

Purchase Online Order Reprints Order Eprints Rights and Permissions


Article Details

Volume: 13
First Page:
Page Count:
DOI: 10.2174/18715206113139990028

Webmaster Contact: Copyright © 2015 Bentham Science