Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: synthesis, cytotoxicity, DNA-binding and cell cycle evaluation.
A family of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid derivatives were synthesized as a result of our efforts to modify a series of acenaphthopyrrole aromatic-heterocycle compounds that proved to be potent anticancer drugs. Among the derivatives, 3d (3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) and 3g (3-piperidine-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) showed potential anticancer activity and different action mechanism from our previously reported compounds. UV-vis absorption, circular dichroism and viscosity measurement indicated that effect of both compounds on the advanced DNA conformation was different, although they could bind to DNA in the same way. Cell cycle analysis showed that 3d could induce S-phase arrest followed by apoptosis, while 3g induced apoptosis. The results seem to imply that different action mechanism could contribute to the dissimilitude of biological activities toward 3d and 3g.
Xie
Lijuan
L
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China.
Xiao
Yi
Y
Wang
Fang
F
Xu
Yufang
Y
Qian
Xuhong
X
Zhang
Rong
R
Cui
Jingnan
J
Liu
Jianwen
J
D000073:Acenaphthenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009690:Nucleic Acid Conformation; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016196:S Phase; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
C545790:3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-(1,2-b)pyrrole-9-carboxylic acid; C545791:3-piperidine-8-oxo-8H-acenaphtho-(1,2-b)pyrrole-9-carboxylic acid; D000073:Acenaphthenes; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011758:Pyrroles; D004247:DNA