Synthesis, cytotoxic activities and DNA binding properties of β-carboline derivatives.
In a continuing effort to develop novel β-carbolines endowed with better pharmacological profile, a series of water-soluble β-carbolines bearing a flexible amino side chain was designed and synthesized, and the cytotoxic activities in vitro of these compounds were evaluated. The N(9)-arylated alkyl substituted β-carbolines represented the most interesting cytotoxic agents, and compounds 4c and 4d were found to be the most potent compounds with IC(50) values lower than 10 μM against ten human tumor cell lines. The results confirmed that the N(9)-arylated alkyl substituents of β-carboline played a very important role in the modulation of the cytotoxic potencies. In addition, the interaction with DNA of these compounds was also investigated, these compounds were found to exhibit significant DNA binding affinity.
Chen
Zhiyong
Z
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Cao
Rihui
R
Yu
Liang
L
Shi
Buxi
B
Sun
Jie
J
Guo
Liang
L
Ma
Qin
Q
Yi
Wei
W
Song
Xiao
X
Song
Huacan
H
D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D002243:Carbolines; D004247:DNA