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N-取代异吲哚啉-1,3-二酮的对接、合成及抗惊厥活性

Docking, Synthesis and Anticonvulsant Activity of N-substituted Isoindoline-1,3-dione.

作者信息

Iman Maryam, Saadabadi Atefeh, Davood Asghar, Shafaroodi Hamed, Nikbakht Ali, Ansari Abdollah, Abedini Masood

机构信息

Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.

出版信息

Iran J Pharm Res. 2017 Spring;16(2):586-595.

Abstract

A series of compounds related to ameltolide were studied for anticonvulsant potential in the subcutaneous pentylenetetrazol (sc Ptz) test in mice. These compounds were synthesized and characterized by TLC followed by IR and HNMR. screening data acquired indicate that most of analogs have the ability to protect against PTZ-induced seizure. Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. All compounds exerted their maximal effects 30 min after administration. Out of the 6 compounds, compound 2 at 40 mg/Kg dose is more potent than phenytoin (reference drug) on clonic seizure. Using a model of the open pore of the Na channel, docking study was performed by AutoDock 4.2 program. Docking study has revealed that these compounds are stabilized through at least one hydrogen bond rises from ketone of phthalimide and residue Thr-87 of domain G of sodium channel.

摘要

研究了一系列与阿美托利德相关的化合物在小鼠皮下注射戊四氮(sc Ptz)试验中的抗惊厥潜力。这些化合物通过薄层色谱法(TLC)合成并表征,随后进行红外光谱(IR)和核磁共振氢谱(HNMR)分析。所获得的筛选数据表明,大多数类似物具有预防戊四氮诱导惊厥的能力。苯妥英(PHT)用作参考原型抗癫痫药物。所有化合物在给药后30分钟发挥最大作用。在这6种化合物中,化合物2在40mg/Kg剂量下对阵挛性惊厥的作用比苯妥英(参考药物)更强。使用钠通道开放孔模型,通过AutoDock 4.2程序进行对接研究。对接研究表明,这些化合物通过至少一个由邻苯二甲酰亚胺的酮基与钠通道G结构域的苏氨酸-87残基形成的氢键得以稳定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be9f/5603866/cf6454c44dc8/ijpr-16-586-g001.jpg

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