• 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>Bioinformation >Computer aided identification of sodium channel blockers in the clinical treatment of epilepsy using molecular docking tools
【2h】

Computer aided identification of sodium channel blockers in the clinical treatment of epilepsy using molecular docking tools

机译：使用分子对接工具的计算机辅助识别在癫痫临床治疗中的钠通道阻滞剂

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

Phenytoin (PHT) and Carbamazepine (CBZ) are excellent sodium channel blockers administered in clinical treatment of epileptic seizures. However, the narrow therapeutic range and limited pharmacokinetics of these drugs have raised serious concerns in the proper management of epilepsy. To overcome this, the present study attempts to identify a candidate molecule with superior pharmacological profile than PHT and CBZ through In silico approaches. PHT and CBZ served as query small molecules for Tanimoto based similarity search with a threshold of 95% against PubChem database. Aided by MolDock algorithm, high affinity similar compound against each query was retrieved. PHT and CBZ and their respective similar were further tested for toxicity profiles, LC 50 values and biological activity. Compounds, NSC403438 and AGN-PC-0BPCBP respectively similar to PHT and CBZ demonstrated higher affinity to sodium channel protein than their respective leads. Of particular relevance, NSC403438 demonstrated highest binding affinity bestowed with least toxicity, better LC 50 values and optimal bioactivity. NSC403438 was further mapped for its structure based pharmacophoric features. In the study, we report NSC403438 as potential sodium channel blocker as a better candidate than PHT and CBZ which can be put forth for pharmacodynamic and pharmacokinetic studies.AbbreviationsAEDs - Antiepileptic drugs, BLAST - Basic Local Alignment Search Tool, CBZ - Carbamazepine, GEFS+ - Generalized Epilepsy with Febrile Seizures Plus, GPCR - G Protein Coupled Receptor, Nav - Sodium channel with specific voltage conduction, PDB - Protein Data Bank,PHT - Phenytoin, PIR - Protein Information resources,SAVES - Structural Analysis and Verification Server,VGSC - Voltage-gated Sodium channels.
机译：苯妥英钠（PHT）和卡马西平（CBZ）是在癫痫发作的临床治疗中使用的极好的钠通道阻滞剂。但是，这些药物的狭窄治疗范围和有限的药代动力学已经引起对癫痫的正确处理的严重关注。为了克服这个问题，本研究试图通过计算机方法鉴定比PHT和CBZ具有更高药理学特性的候选分子。 PHT和CBZ用作基于Tanimoto的相似性搜索的小分子查询，针对PubChem数据库的阈值为95％。在MolDock算法的帮助下，针对每个查询检索了具有高亲和力的相似化合物。进一步测试了PHT和CBZ及其类似物的毒性概况，LC 50值和生物活性。分别类似于PHT和CBZ的化合物NSC403438和AGN-PC-0BPCBP显示出对钠通道蛋白的亲和力高于其各自的前导物。特别相关的是，NSC403438表现出最高的结合亲和力，具有最低的毒性，更好的LC 50值和最佳的生物活性。 NSC403438因其基于结构的药效学特征而被进一步定位。在这项研究中，我们报告了NSC403438作为潜在的钠通道阻滞剂，比PHT和CBZ更好，可以用于药效学和药代动力学研究。全身性癫痫伴高热惊厥，GPCR-G蛋白偶联受体，Nav-具有特定电压传导的钠通道，PDB-蛋白质数据库，PHT-苯妥英钠，PIR-蛋白质信息资源，节省-结构分析和验证服务器，VGSC-电压门控钠通道。

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