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

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 (R2cv = 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.