title: Synthesis of novel beta-carbolines with efficient DNA-binding capacity and potent cytotoxicity.
abstract: 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.
authors.affiliation: Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chen
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Buxi
authors.initials: B
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Huacan
authors.initials: H
authors.lastname: Song
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ren
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D004247:DNA; C427203:calf thymus DNA