Nine chalcone derivatives containing an N-heterocyclic compound attached by its nitrogen atom to one of the benzene rings were prepared and evaluated for their antiproliferative activity against liver, gastric and neuroendocrine cancer cell lines. Most of the synthesised compounds exhibited moderate to good activity against all three cancer cell lines, but in particular, a chalcone containing a 4-(imidazol-1-yl)phenyl group and a 3,4,5-trimethoxyphenyl group showed the highest antiproliferative activity with an IC₅₀ value of 5.39 μM against liver cancer cells.