Synthesis, structural characterization, and cytotoxic evaluation of chalcone derivatives

Chalcones containing amino or acetamide groups on ring A and electron donating/withdrawing groups on ring B have been shown to have great cytotoxic potential against human cancer cell lines. In this work, a series of twenty chalcones, including nine 1-(4 '-aminophenyl)-3-(substituted aryl)-2-propen-1-ones (1-9), nine 1-(4 '-acetamidophenyl)-3-(substituted aryl)-2-propen-1-ones (1a-9a), and two 1-(3 '-methoxy-4 '-hydroxyphenyl)-3-(substituted aryl)-2-propen-1-ones (10, 11), were synthesized and submitted for initial biological screening using HCT-116 cells. Among the evaluated compounds, chalcone 6a showed strong and selective activity against HCT-116 cells (IC50 = 2.37 +/- 0.73 mu M). The preliminary structure-activity relationship analysis indicated that the cytotoxic effect of these compounds might be attributed to the combined effect of two electron withdrawing groups: the nitro group (NO2) at the meta-position of ring B and the acetyl group at the para-position of ring A. Moreover, chalcone 6a was able to induce G2/M cell cycle arrest and apoptosis at a concentration of 10 mu M after 24 h of incubation. These data reinforce that compound 6a could be a promising lead compound for the future exploration of selective anti-colon carcinoma cancer agents.