Issue 22, 2009
From the journal:

Organic & Biomolecular Chemistry

Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway

Zhi-yong Tian,ab   Song-qiang Xie,c   Zi-hou Mei,d   Jin Zhao,a   Wen-yuan Gao*b  and  Chao-jie Wang*a  

* Corresponding authors

a Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng, China
E-mail: wcjsxq@henu.edu.cn
Fax: +86-378-2864665

b School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China
E-mail: pharmgao@tju.edu.cn
Fax: +86-22-87401895
Tel: +86-22-87401895

c College of Pharmacy, Henan University, Kaifeng, China

d Chemistry Department, Henan University, Kaifeng, China

Abstract

Though several naphthalimide derivatives have exhibited antitumor activity in clinical trials, some issues such as toxicity prompted further structural modifications on the naphthalimide backbone. A series of naphthalimides conjugated with polyamines were synthesized to harness the polyamine transporter (PAT) for drug delivery, which was beneficial for the tumor cell selectivity. Bioevaluation in human hepatoma HepG2 cells treated with α-difluoromethylornithine (DFMO) or spermidine (Spd), human hepatoma Bel-7402 and normal QSG-7701 hepatocyte confirmed the PAT recognition and cell selectivity. In addition, the novel naphthalimide polyamine conjugate kills cellsviaapoptosis, and the Akt/mTOR signal pathway was first identified as the upstream cellular target through the apoptotic mechanism research. The presence of DFMO or Spd only either elevated or attenuated the cell apoptosis, but did not change the signal pathway. Collectively, the proper polyamine recognition element (i.e., homospermidine) mediated effective drug delivery via the PAT, and helped the proper cytotoxic goods (i.e., diverse naphthalimides) exert antitumor properties.

Graphical abstract: Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway

About
Cited by
Related
Download options Please wait...

Associated articles

Article information

DOI
https://doi.org/10.1039/B912685F
Article type
Paper
Submitted
29 Jun 2009
Accepted
03 Aug 2009
First published
03 Sep 2009

Org. Biomol. Chem., 2009,7, 4651-4660

Permissions

Request permissions

Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway

Z. Tian, S. Xie, Z. Mei, J. Zhao, W. Gao and C. Wang, Org. Biomol. Chem., 2009, 7, 4651 DOI: 10.1039/B912685F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements