...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Synthesis and Structure-Activity Relationships of Tetrahydro-beta-carboline Derivatives as Anticancer and Cancer-chemopreventive Agents
【24h】

Synthesis and Structure-Activity Relationships of Tetrahydro-beta-carboline Derivatives as Anticancer and Cancer-chemopreventive Agents

机译：四氢β-咔啉衍生物作为抗癌和癌症化学预防剂的合成与结构 - 活性关系

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background/Aim: There is an unmet clinical need to develop new anticancer and chemopreventive agents. The aim of the present study was to identify beta-carboline derivatives with cancer chemopreventive and therapeutic potential. Materials and Methods: Forty-eight tetrahydro-beta-carboline derivatives were synthesized and evaluated for their anticancer and chemopreventive activities, through induction of quinone reductase 1 (QR1), aromatase inhibition, as well as inhibition of nitric oxide (NO) production. Results: 2-(1-Bromonaphthalen-2-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole demonstrated the most potent activity in the QR1 induction assay with an induction ratio value of 3.2 (CD=1.3 mu M). The R-isomer of the amide derivative (2-(1-bromonaphthalen-2-yl)methyl)-2 ,3 ,4,9-tetrahydro-1H-pyrido [3 ,4-b]indol-3-yl)(4-methylpiperazin-1-yl)methanone was the most potent inhibitor of NO production with a 50% inhibitory concentration, IC50 =6.54 mu M and had a low cytotoxic effect (IC50 =17.98 mu M) on RAW 264.7 cells. Subsequent computational docking study revealed that this compound binds to the active site of inducible nitric oxide synthase with favorable interactions. Conclusion: our results provided promising beta-carboline leads for further optimization and development with therapeutic potential as new chemopreventive and chemotherapy agents.
机译：背景/目的：有一个未满足的临床需要开发新的抗癌和化学预防剂。本研究的目的是鉴定具有癌症化学预防和治疗潜力的β-咔啉衍生物。材料和方法：通过诱导醌还原酶1（QR1），芳香酶抑制，以及抑制一氧化氮（NO）生产，合成和评估其抗癌和化学预防活性的抗癌和化学预防活性。结果：2-（1-溴苯萘-2-基）甲基）-2,3,4,9-四氢-1H-吡啶[3,4-B] Indole在QR1诱导测定中显示出最有效的活性，诱导比率值为3.2（CD =1.3μm）。酰胺衍生物的R-异构体（2-（1-溴苯-2-基-2-基）甲基）-2,3,4,9-四氢-1H-吡啶[3,4-B]吲哚-3-基）（ 4-甲基皮哌嗪-1-基）甲基酮是NO生产的最有效的抑制剂，其抑制浓度为50％=6.54μm，并在原料264.7细胞上具有低细胞毒性作用（IC50 =17.98μm）。随后的计算对接研究表明，该化合物与具有良好相互作用的诱导型一氧化氮合酶的活性位点结合。结论：我们的结果提供了有前途的Beta-Carboline，用于进一步优化和开发，作为新化学预防和化疗剂的治疗潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号