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BND-12, a novel nonhaematotoxic naphthalimide derivative, inhibits tumour growth and metastasis of hepatocellular carcinoma.
MedLine Citation:
PMID:  22943179     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Objectives  Naphthalimides have shown potent antitumour activity against a variety of murine and human cancer cells. However, most of them have been abandoned because of a poor therapeutic index and haematotoxicity, such as amonafide. To overcome these disadvantages, many novel naphthalimide derivatives have been designed and synthesized as antitumour agents. Methods  The cytotoxicity of 6,6-(propane-1,3-diylbis(azanediyl)bis(2-(2-(dimethylamino)ethyl)-1H-benzo[de]isoquinoline-1-3(2H)-dione) (BND-12) was evaluated using multiparameter cytotoxicity 2 kit by High Content Screening (HCS). The antiproliferative ability of BND-12 was evaluated using MTT assay. BND-12-mediated cell apoptosis was evaluated using HCS. Antitumor effects and systemic toxicity of BND-12 were evaluated in vivo using Kunming male mice. Key findings  After screening, we found BND-12, a novel naphthalimide derivative, exerted favourable antitumour activity in vitro and in vivo. Our data demonstrated that the cytotoxicity of BND-12 was due to cell apoptosis via the mitochondrial pathway. Interestingly, we demonstrated that BND-12 exerted more potent antitumour activity in subcutaneous xenograft tumour growth, survival time and lung metastasis than amonafide in vivo. Encouragingly, preliminary toxicological evaluation demonstrated that BND-12 had no obvious systemic toxicity at the therapeutic dose, especially haematotoxicity. Conclusions  BND-12 exerted potent effects against HCC in vivo and in vitro, importantly, it had no obvious systemic toxicity at the therapeutic dose.
Authors:
Song-Qiang Xie; Qian Li; Ya-Hong Zhang; Zhan Li; Jin Zhao; Chao-Jie Wang
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Publication Detail:
Type:  Journal Article     Date:  2012-04-23
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  64     ISSN:  2042-7158     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1483-90     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Affiliation:
Institute of Chemical Biology The Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, China.
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