A variety of 3-acyl-2-arylamino-1,4-naphthoquinones were synthesized and evaluated for their antiproliferative activities on a panel of three cancer cells. The designed compounds were prepared from their respective acylhydroquinones by oxidation with silver (I) oxide, followed by amination of the resulting 2-acyl-1,4-naphthoquinones, under aerobic conditions. The donor-acceptor properties of the 2,3-disubstituted 1,4-naphthoquinones were evaluated by means of their first half-wave potentials. The biological screening of the 1,4-quinones showed that the antiproliferative activity depends upon the nature of the substituents at the quinone nucleus. The effect of the substituents on the antiproliferative activity is discussed in terms of their donor-acceptor interactions and lipophilicity.