Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution.
8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild S(N)Ar(H) reaction between 5 and various amines. The biological evaluation indicated that methyl esters 5a are the most cytotoxic with IC(50) values of 0.45 and 0.80 microM (against A549 and P388, respectively) among the parent esters 5a-5f, but 3-amino derivatives 4b and 4c of 5f with bromine showed the highest activity (with IC(50) values of 0.019-0.60 microM) among the 3-amino derivatives.
Liu
Fengyu
F
State Key Laboratory of Fine Chemicals, Dalian University of Technology, China.
Qian
Xuhong
X
Cui
Jingnan
J
Xiao
Yi
Y
Zhang
Rong
R
Li
Gangyue
G
D000073:Acenaphthenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000073:Acenaphthenes; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004952:Esters; D011758:Pyrroles