Synthesis and biological evaluation of novel beta-carbolines as potent cytotoxic and DNA intercalating agents.
A series of novel water-soluble beta-carbolines bearing a flexible amino side chain was designed, synthesized and evaluated as potent cytotoxic and DNA intercatalating agents. The N(9)-arylated alkyl substituted beta-carbolines represented the most interesting cytotoxic activities. The results suggested that (1) the N(9)-arylated alkyl substituents of beta-carboline nucleus played a very important role in the modulation of the cytotoxic potencies; (2) the length of the alkylamino side chain significantly affected their cytotoxic potency, and N,N-dimethylaminopropylamino substituent were more favorable. In addition, these compounds were found to exhibit significant DNA intercalating potencies.
Chen
Zhiyong
Z
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, P. R. China.
Cao
Rihui
R
Shi
Buxi
B
Yi
Wei
W
Yu
Liang
L
Song
Huacan
H
Ren
Zhenhua
Z
D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D009691:Nucleic Acid Denaturation; D013050:Spectrometry, Fluorescence; D044366:Transition Temperature
D002243:Carbolines; D007364:Intercalating Agents; D004247:DNA