• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>EXCLI Journal >Novel inhibitor discovery against aromatase through virtual screening and molecular dynamic simulation: a computational approach in drug design
【2h】

Novel inhibitor discovery against aromatase through virtual screening and molecular dynamic simulation: a computational approach in drug design

机译：通过虚拟筛选和分子动力学模拟发现针对芳香化酶的新型抑制剂：药物设计中的一种计算方法

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Inhibition of aromatase (CYTP450) as a key enzyme in the estrogen biosynthesis could result in regression of estrogen-dependent tumors and even preventing the promotion of breast cancer. Although today potent steroid and non-steroid inhibitors of aromatase are available, isoflavanone derivatives as natural compounds with least side effects have been described as the candidate for a new generation of aromatase inhibitors. 2a as an isoflavanone derivative is the most potent inhibitor of aromatase, synthesized by Bonfield et al. (2012[]). In our computational study, the mentioned compound was used as the template for virtual screening. Between 286 selected compounds with 70 % of structural similarity to 2a, 150 of them showed lower docking energy in comparison with 2a. Compound 2a_1 with 11.2 kcal/mol had the lowest docking energy. Interaction of 2a_1 with aromatase was further investigated and compared with 2a and androstenedione (ASD) as a natural substrate of aromatase, through 20 ns of molecular dynamic simulation. Analysis of trajectories showed, while ASD interacts with aromatase through hydrogen bonds and 2a just interacts via hydrophobic forces, 2a_1 not only accommodates in the hydrophobic active site of aromatase in a suitable manner but it also makes a stable coordination with iron atom of aromatase heme group via OB.
机译：抑制芳香化酶（CYTP450）作为雌激素生物合成中的关键酶可能会导致雌激素依赖性肿瘤消退，甚至阻止乳腺癌的发展。尽管如今有有效的芳香酶类固醇和非类固醇抑制剂可用，但异黄酮衍生物作为具有最小副作用的天然化合物已被描述为新一代芳香酶抑制剂的候选者。 Bonfield等人合成的异黄烷酮衍生物2a是最有效的芳香化酶抑制剂。 （2012 []）。在我们的计算研究中，提到的化合物用作虚拟筛选的模板。在286种与2a具有70％结构相似性的化合物中，其中150种与2a相比具有较低的对接能。具有11.2kcal / mol的化合物2a_1具有最低的对接能。通过20 ns的分子动力学模拟，进一步研究了2a_1与芳香酶的相互作用，并与2a和雄烯二酮（ASD）作为芳香酶的天然底物进行了比较。轨迹分析表明，ASD通过氢键与芳香酶相互作用，而2a只是通过疏水力相互作用，而2a_1不仅以合适的方式容纳在芳香酶的疏水活性位点，而且还与芳香酶血红素基团的铁原子形成稳定的配位。通过OB。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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