Synthesis and cytotoxic evaluation of N2-benzylated quaternary beta-carboline amino acid ester conjugates.
The beta-carboline alkaloids have been characterized as a class of potential antitumor agents. To further enhance the cytotoxic potency and improve water solubility of beta-carboline, a series of new beta-carboline amino acid ester, beta-carboline amino acid and N(2)-benzylated quaternary beta-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were evaluated using a panel of human tumor cell lines. The N(2)-benzylated quaternary beta-carboline amino acid ester conjugates represented the most interesting cytotoxic activities. Particularly, compounds 8b and 8g were found to be the most potent compounds with IC(50) values lower than 20 microM against all human tumor cell lines investigated. These results confirmed that the N(2)-benzyl substituent on the beta-carboline ring played an important role in the modulation of the 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
Li
Shaoxue
S
Chen
Zhiyong
Z
Yi
Wei
W
Peng
Wenlie
W
Ren
Zhenhua
Z
Song
Huacan
H
D000596:Amino Acids / Q000737:chemistry*; D001593:Benzyl Compounds / Q000737:chemistry*; D002243:Carbolines / Q000737:chemistry*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000596:Amino Acids; D001593:Benzyl Compounds; D002243:Carbolines; D004952:Esters