3-Benzylamino-β-carboline derivatives induce apoptosis through G₂/M arrest in human carcinoma cells HeLa S-3

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• 作者：Reiko Ikeda ; Toshie Iwaki ; Tomoko Iida ; Takasumi Okabayashi ; Eishiro Nishi ; Masaki Kurosawa ; Norio Sakai ; Takeo Konakahara
• 关键词：β ; -Carboline ; Anti-tumor activity ; Apoptosis ; Chromatin condensation ; DNA ladder ; G₂/M cell cycle arrest
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：46
• 期：2
• 页码：636-646
• 全文大小：1626 K

文摘

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.