Selectivity profile comparison for certain γ-butyrolactone and oxazolidinone-based ligands on a sigma 2 receptor over sigma 1: a molecular docking approach

• Published in: RSC advances Vol. 12; no. 31; pp. 296 - 219
• Main Authors: Bhandare, Richie R, Sigalapalli, Dilep Kumar, Shaik, Afzal B, Canney, Daniel J, Blass, Benjamin E
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 06.07.2022; The Royal Society of Chemistry
• Subjects: Alzheimer's disease; Butyrolactone; Chemical compounds; Chemistry; Head injuries; Homology; Ligands; Molecular docking; Pharmacology; Receptors; Schizophrenia; Selectivity; Three dimensional models
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d2ra03497b

Sigma receptors (σ 1 R and σ 2 R) are pharmacologically characterized membrane-bound receptors that bind a wide range of chemical compounds. Alzheimer's disease, traumatic brain injury, schizophrenia, and neuropathic pain have all been associated with abnormal σ 2 activity. The σ 2 receptor has recently been identified as a potential therapeutic target for inhibiting the formation of amyloid plaques. Numerous laboratories are now investigating the potential of σ 2 ligands. Small molecule discovery is the focus of current research, with the goal of using target-based action to treat a variety of illnesses and ailments. Functionalized γ-butyrolactone and oxazolidinone-based ligands, in particular, are pharmacologically important scaffolds in drug discovery research and have been thoroughly examined for σ 2 receptor efficacy. The purpose of this study was to evaluate the pharmacophoric features of different σ 2 receptor ligands using in silico techniques. This study used a library of 58 compounds having a γ-butyrolactone and oxazolidinone core. To investigate the binding characteristics of the ligands with the σ 2 receptor, a 3D homology model was developed. To understand the binding pattern of the γ-butyrolactone and oxazolidinone based ligands, molecular docking studies were performed on both σ 1 and σ 2 receptors. Furthermore, MM/GBSA binding energy calculations were used to confirm the binding of ligands on the σ 2 over σ 1 receptor. These in silico findings will aid in the discovery of selective σ 2 ligands with good pharmacophoric properties and potency in the future. Selective action of γ-butyrolactones and oxazolidinones towards σ 2 receptor.