title: Design of beta-carboline derivatives as DNA-targeting antitumor agents.
abstract: This research studied the structure-activity relationship of beta-carboline derivatives as antitumor agents, in which 41 synthesized compounds and their cytotoxicity to tumor and normal cell lines were assayed. It was proved that substituent in position-9 of the beta-carboline ring could reinforce the DNA intercalating ability and consequently cytotoxicity to tumor cell lines, and the amidation of amino group at the end of the DNA targeting side chain in position-3 could cripple the DNA intercalating activity of these compounds, which resultingly initiated the cytotoxic selectivity to tumor cell lines rather than to normal ones. Furthermore, the S and G2-M arrest induced by these compounds confirmed that they could target DNA and lead to DNA destructions in Hela cells. In short, this study may provide a framework to design a novel antitumor drug that could surpass Adriamycin.
authors.affiliation: State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Therapeutic Functional Genes, Department of Biochemistry, College of Life Sciences, Sun Yat-sen (Zhongshan) University, 135, Xin Gang Xi Road, Guangzhou 510275, China.
authors.forename: Huaji
authors.initials: H
authors.lastname: Guan
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D015394:Molecular Structure; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D004247:DNA