Investigation of Hydantoin-Based Drugs Used in the Treatment of Epilepsy Using Quantum Chemical Calculations, Molecular Docking, Molecular Dynamics, ADMET, In Vitro, and Spectroscopic Methods

IF 2.3 3区 化学 Q3 CHEMISTRY, PHYSICAL International Journal of Quantum Chemistry Pub Date : 2024-09-26 DOI:10.1002/qua.27485
Minnet Can Kandemir, Bilge Bicak, Serda Kecel-Gunduz, Gizem Akman
{"title":"Investigation of Hydantoin-Based Drugs Used in the Treatment of Epilepsy Using Quantum Chemical Calculations, Molecular Docking, Molecular Dynamics, ADMET, In Vitro, and Spectroscopic Methods","authors":"Minnet Can Kandemir,&nbsp;Bilge Bicak,&nbsp;Serda Kecel-Gunduz,&nbsp;Gizem Akman","doi":"10.1002/qua.27485","DOIUrl":null,"url":null,"abstract":"<p>Present investigation deals with the structural and pharmacokinetic properties of hydantoin-based drug molecules such as phenytoin, mephenytoin, and ethotoin. Hydantoin-based drugs are widely used as anticonvulsants in the treatment of epilepsy. In this study, optimized structures, and theoretical vibrational wavenumbers of phenytoin, mephenytoin, and ethotoin molecules were determined using Gaussian 09 program with density functional theory (DFT) and B3LYP/6-311++G(d,p) basis set, vibration mode assignments were performed with the GAR2PED program, and the theoretical results were supported by FTIR and Raman spectroscopy. In addition, thermodynamic parameters, Mulliken charge values, HOMO-LUMO, natural bond orbital, MEP, hyperpolarizability analyzes of hydantoin-based molecules were performed. Docking analysis of all molecules with the GABA-AT receptor, which has an important place in epilepsy studies, were also carried out. Then, the molecular dynamic (MD) simulations of the hydantoin-based drugs-GABA-AT complexes were realized for 50 ns. ADMET profiles of all molecules were determined and presented by parameters of toxicity and drug-likeness. Additionally, to determine the effects of hydantoin-based drugs on glioblastoma cells, cytotoxic effects of phenytoin, mephenytoin, and ethotoin were evaluated on U-87 Human glioblastoma cell line.</p>","PeriodicalId":182,"journal":{"name":"International Journal of Quantum Chemistry","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/qua.27485","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Quantum Chemistry","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/qua.27485","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0

Abstract

Present investigation deals with the structural and pharmacokinetic properties of hydantoin-based drug molecules such as phenytoin, mephenytoin, and ethotoin. Hydantoin-based drugs are widely used as anticonvulsants in the treatment of epilepsy. In this study, optimized structures, and theoretical vibrational wavenumbers of phenytoin, mephenytoin, and ethotoin molecules were determined using Gaussian 09 program with density functional theory (DFT) and B3LYP/6-311++G(d,p) basis set, vibration mode assignments were performed with the GAR2PED program, and the theoretical results were supported by FTIR and Raman spectroscopy. In addition, thermodynamic parameters, Mulliken charge values, HOMO-LUMO, natural bond orbital, MEP, hyperpolarizability analyzes of hydantoin-based molecules were performed. Docking analysis of all molecules with the GABA-AT receptor, which has an important place in epilepsy studies, were also carried out. Then, the molecular dynamic (MD) simulations of the hydantoin-based drugs-GABA-AT complexes were realized for 50 ns. ADMET profiles of all molecules were determined and presented by parameters of toxicity and drug-likeness. Additionally, to determine the effects of hydantoin-based drugs on glioblastoma cells, cytotoxic effects of phenytoin, mephenytoin, and ethotoin were evaluated on U-87 Human glioblastoma cell line.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
利用量子化学计算、分子对接、分子动力学、ADMET、体外和光谱方法研究用于治疗癫痫的海因类药物
目前的研究涉及苯妥英、甲苯妥英和乙托品等以海因为基础的药物分子的结构和药代动力学特性。海因类药物被广泛用作治疗癫痫的抗惊厥药。本研究利用密度泛函理论(DFT)的高斯 09 程序和 B3LYP/6-311++G(d,p) 基集确定了苯妥英、甲苯妥英和乙妥英分子的优化结构和理论振动波数,利用 GAR2PED 程序进行了振动模式分配,并利用傅立叶变换红外光谱和拉曼光谱支持了理论结果。此外,还对基于海因的分子进行了热力学参数、Mulliken 电荷值、HOMO-LUMO、自然键轨道、MEP 和超极化分析。还对所有分子与 GABA-AT 受体(在癫痫研究中占有重要地位)进行了对接分析。然后,对基于海因的药物-GABA-AT 复合物进行了 50 ns 的分子动力学(MD)模拟。确定了所有分子的 ADMET 特征,并通过毒性和药物亲和性参数进行了展示。此外,为了确定海因类药物对胶质母细胞瘤细胞的影响,还评估了苯妥英、甲苯妥英和乙托品对 U-87 人类胶质母细胞瘤细胞系的细胞毒性作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
International Journal of Quantum Chemistry
International Journal of Quantum Chemistry 化学-数学跨学科应用
CiteScore
4.70
自引率
4.50%
发文量
185
审稿时长
2 months
期刊介绍: Since its first formulation quantum chemistry has provided the conceptual and terminological framework necessary to understand atoms, molecules and the condensed matter. Over the past decades synergistic advances in the methodological developments, software and hardware have transformed quantum chemistry in a truly interdisciplinary science that has expanded beyond its traditional core of molecular sciences to fields as diverse as chemistry and catalysis, biophysics, nanotechnology and material science.
期刊最新文献
Exploring Chlorinated Solvents as Electrolytes for Lithium Metal Batteries: A DFT and MD Study Dihydro-1H-Pyrazoles as Donor Blocks in Donor–Acceptor Chromophores for Electro-Optics: A DFT Study of Hyperpolaizability and Electronic Excitations Evaluating Electronic Properties of Self-Assembled Indium Phosphide Nanomaterials as High-Efficient Solar Cell Generation of Database of Polymer Acceptors and Machine Learning-Assisted Screening of Efficient Candidates DFT Computation, Spectroscopic, Hirshfeld Surface, Docking and Topological Analysis on 2,2,5-Trimethyl-1,3-Dioxane-5-Carboxylic Acid as Potent Anti-Cancer Agent
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1