Synthesis of new amonafide analogues via coupling reaction and their cytotoxic evaluation and DNA-binding studies.
A series of 5-alkylamino substituted amonafide analogues were synthesized from naphthalic anhydride by three steps including bromization, amination and CuI/proline catalyzed coupling reaction. The CuI/L-proline catalyzed coupling reaction was first applied to the naphthalimide system. These new amonafide analogues showed potential anticancer activities against HeLa and P388D1 cell lines in vitro, and 4a, 4b, and 4h exhibited better activity than amonafide against HeLa cell under the same experimental conditions. More importantly, the new analogues could avoid the side effect of amonafide due to their structure, in which lacks a primary amine at the 5 position. Moreover, the DNA-binding of the analogues was also investigated.
Xie
Lijuan
L
State Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 89, Zhongshan Road 158, Dalian 116012, China.
Xu
Yufang
Y
Wang
Fang
F
Liu
Jianwen
J
Qian
Xuhong
X
Cui
Jingnan
J
D000225:Adenine; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry; D053644:Naphthalimides / Q000138:chemical synthesis* / Q000494:pharmacology; D063065:Organophosphonates; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009281:Naphthalenes; D053644:Naphthalimides; D063065:Organophosphonates; C037020:amonafide; C012514:1,8-naphthalenedicarboxylic acid anhydride; D004247:DNA; D000225:Adenine