Scholarlink

<p>Carbazoles exhibit various pharmacological activities, including antitumor activity. Eustifoline-B is a carbazole from <i>Murraya</i> (Rutaceae) plants that exhibited strong antiproliferative activity against cancer stem cells (CSCs) that were established from a human glioblastoma (GBM) cell line (U-251 MG). This activity was stronger than that against GBM cells (non-CSCs), indicating that the activity was CSCs-selective. In this study, the efficacy of carbazole derivatives against GBM was evaluated, their structure–activity relationships were examined, and their blood–brain-barrier (BBB) permeability was investigated in vitro. First, 26 carbazole derivatives, two indole derivatives, and two quinoline derivatives were synthesized, including 12 new compounds. Next, 34 compounds, including the synthesized carbazole derivatives, were evaluated for their antiproliferative activities against U-251 MG CSCs and non-CSCs. Carbazoles with prenyl groups, including eustifoline-B, showed concentration-dependent antiproliferative activity against U-251 MG CSCs (IC<sub>50</sub> = 3.5–19.8&#xa0;µM). Among the prenyl groups, carbazole derivatives with geranyl groups, such as eustifoline-B and eustifoline-C, tended to have stronger activity against CSCs (IC<sub>50</sub> = 6.2&#xa0;µM and 3.5&#xa0;µM) than that against non-CSCs (IC<sub>50</sub> &gt; 25&#xa0;µM and IC<sub>50</sub> = 6.6&#xa0;µM), indicating that they are CSCs-selective. Finally, in vitro BBB permeability studies were performed using six carbazoles; most carbazoles, including eustifoline-C, exhibited BBB permeability. These results suggest the promising potential of carbazoles as new pharmaceutical agents for the treatment of GBM.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Antiproliferative activity against glioblastoma-derived cancer stem cells and blood–brain-barrier permeability of carbazole derivatives from Murraya plants and related synthetic compounds

  • 期刊论文

  • 发表日期：

    2025年10月15日

查看全文
  • Kouta Ugawa,
  • Raiki Yamamura,
  • Kaori Yajima,
  • Tomoe Ohta,
  • Seikou Nakamura

摘要

Carbazoles exhibit various pharmacological activities, including antitumor activity. Eustifoline-B is a carbazole from Murraya (Rutaceae) plants that exhibited strong antiproliferative activity against cancer stem cells (CSCs) that were established from a human glioblastoma (GBM) cell line (U-251 MG). This activity was stronger than that against GBM cells (non-CSCs), indicating that the activity was CSCs-selective. In this study, the efficacy of carbazole derivatives against GBM was evaluated, their structure–activity relationships were examined, and their blood–brain-barrier (BBB) permeability was investigated in vitro. First, 26 carbazole derivatives, two indole derivatives, and two quinoline derivatives were synthesized, including 12 new compounds. Next, 34 compounds, including the synthesized carbazole derivatives, were evaluated for their antiproliferative activities against U-251 MG CSCs and non-CSCs. Carbazoles with prenyl groups, including eustifoline-B, showed concentration-dependent antiproliferative activity against U-251 MG CSCs (IC50 = 3.5–19.8 µM). Among the prenyl groups, carbazole derivatives with geranyl groups, such as eustifoline-B and eustifoline-C, tended to have stronger activity against CSCs (IC50 = 6.2 µM and 3.5 µM) than that against non-CSCs (IC50 > 25 µM and IC50 = 6.6 µM), indicating that they are CSCs-selective. Finally, in vitro BBB permeability studies were performed using six carbazoles; most carbazoles, including eustifoline-C, exhibited BBB permeability. These results suggest the promising potential of carbazoles as new pharmaceutical agents for the treatment of GBM.

Graphical Abstract