title: 3-benzylamino-β-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3.
abstract: β-carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of β-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-β-carboline, and evaluated their anti-tumor activity for HeLa S-3 cell line. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that an optimal structure for anti-tumor activity was 3-cyclohexylmethylamino (1e) or 3-benzylamino-β-carboline (1f). An optimal counter anion of 2-methyl-3-benzylamino- β-carbolinium salts was a triflate anion 2c. In addition, the introduction of a hydroxyl group on the meta-position of the benzyl group of 3-benzylamino-β-carboline (3e) enhanced its anti-tumor activity. Hoechst 33342 staining and DNA fragmentation assay suggested that 1f, 2c and 3e induced cell death by apoptosis unlike 1e. Flow cytometry analysis showed that 1f, 2c and 3e induced cell apoptosis through arrest of the cell cycle in the G2/M phase.
authors.affiliation: Department of Pure and Applied Chemistry, Faculty of Science and Technology, Center for Technologies against Cancer, Tokyo University of Science (RIKADAI), Noda, Chiba, 278-8510, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ikeda
authors.forename: Toshie
authors.initials: T
authors.lastname: Iwaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Iida
authors.forename: Takasumi
authors.initials: T
authors.lastname: Okabayashi
authors.forename: Eishiro
authors.initials: E
authors.lastname: Nishi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kurosawa
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.forename: Takeo
authors.initials: T
authors.lastname: Konakahara
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C558522:3-benzylamino-beta-carboline; D000970:Antineoplastic Agents; D002243:Carbolines