作为潜在的抗癌剂的新型D-修饰的异环性安德罗斯坦衍生物:合成,表征,体外和体内研究
Tijana Lj Šestić1, Jovana J Ajduković1, Sofija S Bekić1
1Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
概括
新的类固醇激素衍生品在癌症研究中表现有前途. 化合物9A表现出选择性的抗癌活性,而其他化合物则针对特定的激素受体和参与癌症进展的酶.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 癌症生物学 癌症生物学
背景情况:
- 类固醇激素在荷尔蒙依赖性癌症中起着至关重要的作用.
- 异常的类固醇激素产生或作用是癌症发展的主要驱动因素.
- 需要针对类固醇激素途径的新型治疗策略.
研究的目的:
- 合成和结构性表征新型异环氨衍生物.
- 评估这些化合物的抗癌细胞系的抗增殖活性.
- 研究它们作为激素受体和酶抑制剂的选择性联结体的潜力.
主要方法:
- 新型安德罗斯坦衍生物的合成与D-homo乳和皮里丁部分.
- 在实验室中使用HeLa宫癌和MDCK脏细胞系进行的抗增殖试验.
- 对于雌激素受体α (ERα),葡萄糖皮质体受体结合体结合域 (GR-LBD) 和芳酶的体外结合测试.
- 对阿尔多-基托减少酶1C4.4.的酶抑制试验.
- 在体研究中进行蛋白质-体相互作用分析.
主要成果:
- 与MDCK细胞相比,化合物9A对HeLa细胞具有最高的选择性.
- 化合物18被确定为ERα的强效和异型选择性联结体.
- 化合物9A对GR-LBD表现出结合亲和力,并抑制了阿尔多基因还原酶1C4.4.
- 化合物13表明具有结合芳香酶的潜力.
- 在 silico 研究证实了关于蛋白质 - 配体相互作用的实验发现.
结论:
- 合成的安德罗斯坦衍生物具有与癌症治疗相关的多种生物活性.
- 化合物9A显示出作为选择性抗癌剂的潜力.
- 特定的衍生品向关键蛋白质,如ERα,GR-LBD,芳酶和阿尔多基因还原酶1C4.4.
- 这些化合物代表了一个有希望的新类药物,用于向与激素相关的癌症.
相关概念视频
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
01:25Mutagenicity and Carcinogenicity
1.3K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
02:15M-Cdk Drives Transition Into Mitosis
5.6K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K