Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted β-carbolines.
The condensation of alkylenediamine with ethyl β-carboline-1-carboxylate and 1-bromo-β-carboline gave β-carboline-1-carboxamides and 1-amino-β-carbolines, respectively. Some of these β-carbolines were active against a panel of human tumor cell lines, and 1-amino derivatives were more potent than their 1-carboxamide congeners. In particular, among the 1-amino-β-carbolines, the N(9)-arylated alkyl substituted β-carbolines exhibited the most interesting cytotoxic activities with IC(50) value of lower than 20 μM. The preliminary structure-activity relationships (SARs) analysis suggested that (1) 1-amino substituents were the advisable pharmacophoric group for enhanced cytotoxic activities; (2) the introduction of appropriate arylated alkyl groups into position-9 of β-carboline facilitated their cytotoxic potencies.
Ma
Chunming
C
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Cao
Rihui
R
Shi
Buxi
B
Zhou
Xiantai
X
Ma
Qin
Q
Sun
Jie
J
Guo
Liang
L
Yi
Wei
W
Chen
Zhiyong
Z
Song
Huacan
H
D000577:Amides / Q000737:chemistry*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000577:Amides; D002243:Carbolines