In silico insight into Amurensinine - an N-Methyl-D-Aspartate receptor antagonist  

作　　者：Cinthia Façanha Wendel Queren Hapuque Oliveira Alencar Rafaela Viana Vieira Kádima Nayara Teixeira 

机构地区：[1]Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular-Setor Palotina,Universidade Federal do Paraná,Palotina 85.950-000,Paraná,Brazil

出　　处：《World Journal of Pharmacology》2023年第3期25-34,共10页世界药理学杂志

摘　　要：BACKGROUND Some isopavines can exhibit important biological activity in the treatment of neurological disorders since it is considered an antagonist of the specific Nmethyl-D-Aspartate(NMDA)receptor.Amurensinine is an isopavine which still has few studies.In view of the potential of isopavines as NMDA receptor antagonists,theoretical studies using bioinformatics were carried out in order to investigate whether Amurensinine binds to the NMDA receptor and to analyze the receptor/Ligand complex.This data can contribute to understanding of the onset of neurological diseases and contribute to the planning of drugs for the treatment of neurological diseases involving the NMDA receptor.AIM To investigate the interaction of the antagonist Amurensinine on the GluN1A/GluN2B isoform of the NMDA receptor using bioinformatics.METHODS The three-dimen-sional structure of the GluN1A/GluN2B NMDA receptor was selected from the Protein Data Bank(PDB)-PDB:4PE5,and the three-dimensional structure of Amurensinine(ligand)was designed and optimized using ACD/SchemsketchTM software.Prediction of the protonation state of Amurensinine at physiological pH was performed using MarvinSketch software(ChemAxon).Protonated and non-protonated Amurensin were prepared using AutoDock Tools 4 software and simulations were performed using Autodock Vina v.1.2.0.The receptor/Ligand complexes were analyzed using PyMol(Schrödinger,Inc)and BIOVIA Discovery Studio(Dassault Systemes)software.To evaluate the NMDA receptor/Amurensinine complex and validate the molecular docking,simulations using NMDA receptor and Ifenprodil antagonist were performed under the same conditions.Ifenprodil was also designed,optimized and protonated,under the same conditions as Amurensinine.RESULTS Molecular docking simulations showed that both non-protonated and protonated Amurensinine bind to the amino terminal domain(ATD)domain of the GluN1A/GluN2B NMDA receptor with significant affinity energy,-7.9 Kcal/mol and-8.1 Kcal/mol,respectively.The NMDA receptor/non-protonated Amurensi

关 键 词：Amurensinine Bioinformatics analysis Isopavines Molecular docking N-methyl-D-Aspartate receptor 

分 类 号：R74[医药卫生—神经病学与精神病学]