Affiliation:
1. Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang-110016, P.R. China
2. Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, School of Pharmaceutical Engineering,
Shenyang Pharmaceutical University, Shenyang-110016, P.R. China
Abstract
Background:
Naphthalimides have been receiving continuous attention for their outstanding
performance in treating cancer. However, as a class of cytotoxic anti-tumor agents, their toxic side effects
greatly limit their clinical application. Therefore, developing naphthalimide reagents with good selectivity
for tumor cells is of great importance.
Methods:
A class of TEMPO-modified naphthalimide derivatives substituted with oxygen at the 6-
position were designed, synthesized, and evaluated for the anti-tumor activity in vitro against three cancer
cell lines (A549, MCF-7, and HeLa) as well as one normal human liver cell line (QSG-7701) by MTT
assay. HRMS (or MS) and EPR spectra were used to identify the structures of target compounds. The
UV–vis titration absorption spectra were performed to study the interaction between compounds and
DNA.
Results:
The target compounds NT3, NT9, NT10, NT11, and NT12 exhibited moderate inhibition to all
the three tested tumor cell lines, while NT1, NT2, and NT4 showed selectivity against A549, All the target
compounds did not show measurable activities in QSG-7701, which imply the target compounds are
likely to overcome the nonspecific toxicity against normal cells. UV-vis spectra showed this class of
compounds could effectively intercalate into DNA and selectively bind to G-C base pairs.
Conclusion:
A novel class of TEMPO-modified naphthalimide derivatives substituted with oxygen at 6-
position and the preliminary discussion on their SARs provide promising opportunities to guide further
research on naphthalimide derivatives as anti-tumor agents.
Funder
Educational Department of Liaoning Province
Career Development Support Plan for Young and Middle-aged Teachers at Shenyang Pharmaceutical University
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine