MIT. College of Pharmacy, Ram Ganga Bihar Phase, Moradabad, 244001, Uttar Pradesh, India.
Department of Pharmaceutical Chemistry, Dr. A.P.J. Abdul Kalam Technical University, Lucknow, 226031, Uttar Pradesh, India.
Curr Comput Aided Drug Des. 2024;20(6):822-834. doi: 10.2174/1573409920666230817144710.
Epilepsy is a chronic neurological disorder caused by irregular electrical activity in the brain. To manage this disorder effectively, it is imperative to identify potential pharmacological targets and to understand the pathophysiology of epilepsy in depth.
This research aimed to identify promising leads from a library of 1,2,4-triazine-6Hindolo[ 2,3-b]quinoline derivatives and optimize them using and dynamic processes.
We used computational studies to examine 1,2,4-Triazine-6H-indolo[2,3-b]quinoline derivatives. Some methods were used to strengthen the stability of binding sites, including Docking, ADMET, IFD, MMGBSA, Density Functional Theory (DFT), and Molecular Dynamics.
HRSN24 and HRSN34 exhibited promising pharmacokinetic and pharmacodynamic characteristics compared to standard drugs (Carbamazepine and Phenytoin) and a co-crystal ligand (Diazepam). Both HRSN24 and HRSN34 presented notable Glide Xp docking scores (-4.528 and -4.633 Kcal/mol), IFD scores (-702.22 and -700.3 Kcal/mol), and MMGBSA scores (-45.71 and -14.46 Kcal/mol). HRSN24 was selected for molecular dynamics and DFT analysis. During MD, HRSN24 identified LYS21, GLY22, ASP24, ARG26, VAL53, MET55, and SER308 as the most important amino acid residues for hydrophobic interactions. A DFT computation was performed to determine the physicochemical properties of HRSN24, revealing a total energy of -1362.28 atomic units, a HOMO value of -0.20186, and a LUMO value of -0.01915.
Based on computational modelling techniques, an array of 1,2,4-triazine-6H-indolo [2,3-b]quinoline derivatives were evaluated for their anti-convulsant properties. A stable compound within the GABAA receptor was identified by HRSN24, suggesting its affinity as an anti-convulsant.
癫痫是一种由大脑中不规则电活动引起的慢性神经系统疾病。为了有效管理这种疾病，必须确定潜在的药物靶点，并深入了解癫痫的病理生理学。
本研究旨在从 1,2,4-三嗪-6H-吲哚并[2,3-b]喹啉衍生物库中鉴定有前途的先导化合物，并使用 和动态过程对其进行优化。
我们使用计算研究来检查 1,2,4-三嗪-6H-吲哚并[2,3-b]喹啉衍生物。使用了一些方法来增强结合部位的稳定性，包括对接、ADMET、IFD、MMGBSA、密度泛函理论（DFT）和分子动力学。
与标准药物（卡马西平和苯妥英）和共晶配体（地西泮）相比，HRSN24 和 HRSN34 表现出有前途的药代动力学和药效学特征。HRSN24 和 HRSN34 的 Glide Xp 对接评分（-4.528 和-4.633 Kcal/mol）、IFD 评分（-702.22 和-700.3 Kcal/mol）和 MMGBSA 评分（-45.71 和-14.46 Kcal/mol）都很显著。选择 HRSN24 进行分子动力学和 DFT 分析。在 MD 过程中，HRSN24 确定了 LYS21、GLY22、ASP24、ARG26、VAL53、MET55 和 SER308 为对疏水相互作用最重要的氨基酸残基。进行了 DFT 计算以确定 HRSN24 的物理化学性质，显示总能量为-1362.28 原子单位、HOMO 值为-0.20186 和 LUMO 值为-0.01915。
基于计算建模技术，评估了一系列 1,2,4-三嗪-6H-吲哚并[2,3-b]喹啉衍生物的抗惊厥特性。通过 HRSN24 鉴定了 GABA A 受体中的稳定化合物，表明其作为抗惊厥剂的亲和力。
