Evaluation of antagonist activity of Ifenprodil and their analogous against GluN1/GluN2B using In-Silico Molecular docking and ADME Toxicity

Abstract

High Ca2+ permeability represents a characteristic feature of NMDA receptors on extreme amounts effects physiological functions like reduce neural development, synaptic plasticity and learning and memory. The study aims to elucidate the potent inhibitory Ifenprodil and their eleven analogues were retrieved from PubChem database which acts as ligands to the target Glun1/GluN2B subunit of NMDA receptor. In silico methods like Molecular docking performed using Autodock Vina and Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) were SwissADME and OSIRIS carried out to elucidate the potent antagonist ligand against target. Molecular docking results showed that six of compounds had remarkable binding affinities (-7.8 to -9.0 kcal/mol) for target. ADMET study revealed that three (PubChemID:12613159, 12613162 and 6604117 of six compounds with good binding affinity and obeyed Lipinski’s rule of five. Hence, they were compounds with inhibitory functions. Therefore, this study revealed three good antagonists of GluN1/GluN2B viz. 4-[(1R,2R)-2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl] phenol(A2),
4-[2-(4-benzylpiperidin-1-yl)-1-hydrooxypropyl] phenol; hydrobromide (A4) and 4-[(1R,2S)-2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl] phenol(A7), that can be further exploited for wet lab studies.