Synthesis and Antitumor Activity of Novel Nitrogen Mustard-Linked Chalcones

A series of nitrogen mustard-linked chalcones were synthesized and evaluated for their antitumor activity in vitro against the K562 and HepG2 cell lines. The aldol condensation of [N,N-bis(chloroethyl)-3-amino]-acetophenone (2) with aromatic aldehydes afforded the nitrogen mustard-linked chalcones. Among the analogs tested, compounds 5e and 5k exhibited significant anti-proliferation activities against K562 cells with IC50 values of 2.55 and 0.61 mu M, respectively, which revealed higher cell toxicity than the standard drugs cisplatin (IC50>200 mu M) and adriamycin (IC50=14.88 mu M). The methoxyl and N,N-dimethyl groups on the B-ring of the chalcone frame enhanced the inhibitory activities against both the K562 and HepG2 cell lines. The structureactivity relationship study indicated that the inhibitory activities significantly varied with the position(s) and species of the substituted group(s).