Novel DNA intercalators without basic side chains as efficient antitumor agents: design, synthesis and evaluation of benzo-[c,d]-indol-malononitrile derivatives.
Several 2-(substituted benzo[c,d]indol-2(1H)-ylidene)malononitriles have been designed and synthesized. Their DNA binding, antitumor and DNA damaging properties were evaluated. All the compounds exhibited efficient antitumor activities with preference to be against the tumor cell line 7721 rather than the tumor cell line MCF-7. Compound 1f could intercalate into DNA entirely presumably by the good conjugation of carbonyl group with benzo[c,d]indol moiety. What's more, 1f exhibited potent toxicity against MCF-7 cells with IC(50) at 0.003 microM and against 7721 cells at 0.115 microM, respectively.
Li
Xiaolian
X
State Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 89, 158 Zhongshan Road, Dalian 116012, China.
Wang
Qianqian
Q
Qing
Yang
Y
Lin
Yanjie
Y
Zhang
Yingli
Y
Qian
Xuhong
X
Cui
Jingnan
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D007211:Indoles; D007364:Intercalating Agents; D009570:Nitriles; D004247:DNA; C427203:calf thymus DNA; C000945:dicyanmethane