Synthesis and antitumor activity of novel nitrogen mustard-linked chalcones

Article abstract of DOI:10.1002/ardp.201200443

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 μM, respectively, which revealed higher cell toxicity than the standard drugs cisplatin (IC₅₀ > 200 μM) and adriamycin (IC₅₀ = 14.88 μM). 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 structure-activity relationship study indicated that the inhibitory activities significantly varied with the position(s) and species of the substituted group(s). A series of nitrogen mustard-linked chalcones were prepared and evaluated for their antitumor activities against the K562 and HepG2 cell lines. The structure-activity relationship study indicated that the methoxyl and N,N-dimethyl groups on the B-ring of the chalcone frame may enhance the inhibitory activities of the chalcones. Copyright