title: Synthesis and antitumor activity of novel nitrogen mustard-linked chalcones.
abstract: 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).
authors.affiliation: Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, Department of Chemistry and Materials Science, Northwest University, Xi'an, PR China. fxw325@126.com
authors.forename: Xianwen
authors.initials: X
authors.lastname: Fang
authors.forename: Bingqin
authors.initials: B
authors.lastname: Yang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Cheng
authors.forename: Meipan
authors.initials: M
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Su
authors.forename: Lizhen
authors.initials: L
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D009588:Nitrogen Mustard Compounds; D004317:Doxorubicin; D002945:Cisplatin