Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2538–2546 | Cite as

Design, synthesis, antitumor evaluation, 3D-QSAR and molecular docking studies of novel 4-aminoacridone compounds

Original Research


4-aminoacridone was efficiently synthesized using an optimized method and condensed with a variety of different aldehydes to give the corresponding Schiff bases, 1a–k. The antiproliferative activities of these compounds were measured against several human cancer cell lines in vitro, including A549, HeLa, SGC-7901, and Raji cells. The results of these bioassays indicate that these compounds possess antiproliferative activity for the HeLa and Raji cell lines. In particular, compounds 1d and 1k containing 4-(N,N-dimethyl)phenyl and 2,4-dichlorophenyl groups, respectively, showed greater potency and selectivity towards HeLa cells than any of the other cell lines (IC50 = 7.75 and 8.88 μM, respectively). Three-dimensional contour maps based on highly predictive 3D-quantitative structure–activity relationship studies (R 2 cv = 0.674, R = 0.956) are used to explain the structure-activity relationships of these compounds. Furthermore, docking studies were conducted to evaluate the multidrug resistance modulatory effects of these imine compounds in the adenosine tri-phosphate binding site of P-glycoprotein and the transmembrane binding pocket. These docking experiments revealed the occurrence of important interactions between these molecules and the active site of the transmembrane binding pocket, predicting multidrug resistance modulatory behavior.


4-aminoacridone derivative Antitumor activity 3D-QSAR Multidrug resistance (MDR) modulator Docking analysis 



Lin Tian thanks Gui F. Dai, Zhengzhou University, Zhengzhou, for testing the activity of the compounds. The authors thank the Chinese National Natural Science Foundation (31270577).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1953_MOESM1_ESM.doc (112 kb)
Supplementary Information
44_2017_1953_MOESM2_ESM.rtf (14 kb)
Supplementary Information
44_2017_1953_MOESM3_ESM.doc (2.1 mb)
Supplementary Information


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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.School of Chemical Engineering and TechnologyChina University of Mining & TechnologyXuzhouChina
  2. 2.School of Chemical Engineering and TechnologyXuzhou Institute of TechnologyXuzhouChina
  3. 3.School of Food Science and TechnologyXuzhou Institute of TechnologyXuzhouChina
  4. 4.School of Chemical Engineering and TechnologyJiangsu Normal UniversityXuzhouChina

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