Synthesis of novel beta-carbolines with efficient DNA-binding capacity and potent cytotoxicity.
A series of water-soluble beta-carbolines, bearing a flexible amino side chain, was prepared and evaluated in vitro against a panel of human tumor cell lines. The N(9)-arylated alkyl substituted beta-carbolines represented the most interesting cytotoxic activities, and compound 7b was found to be the most potent antitumor agent with IC(50) values lower than 10microM against eight human tumor cell lines. The results confirmed that the N(9)-arylated alkyl substituents of beta-carboline nucleus played an important role in the modulation of the cytotoxic potencies. In addition, these compounds were found to exhibit significant DNA-binding affinity.
Chen
Zhiyong
Z
Sun Yat-sen University, Guangzhou, PR China.
Cao
Rihui
R
Shi
Buxi
B
Yi
Wei
W
Yu
Liang
L
Song
Huacan
H
Ren
Zhenhua
Z
Peng
Wenlie
W
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002243:Carbolines; D004247:DNA; C427203:calf thymus DNA